Selective hydrodeoxygenation of aromatic compounds

ABSTRACT

Disclosed are methods of selective hydrodeoxygenation of aromatic compounds by using catalyst systems comprising N-heterocyclic carbene (NHC) and 4-pyridinol-derived pincer ligands and metal complexes containing these ligands.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.62/955,067, filed Dec. 30, 2019, the content of which is incorporatedherein by reference in its entirety.

STATEMENT ACKNOWLEDGING GOVERNMENT SUPPORT

This invention was made with government support under Grant No.CHE-1800214, Grant No. OIA-1539035, and Grant No. OIA-15939105, allawarded by the National Science Foundation. The government has certainrights in the invention.

BACKGROUND

Total world energy consumption was 575 quadrillion Btu in 2015, and itis predicted to increase by 285 to 736 quadrillion Btu in 2040 (USEnergy_Information_Administration International Energy Outlook 2017). Inaddition, renewable fuels are predicted to be the world'sfastest-growing energy source, with consumption increasing by an averageof 2.3% per year between 2015 and 2040. Renewables contributed 19% tothe total energy consumption in 2012(Renewable_Energy_Policy_Network_for_21st_Century Renewables 2014 GlobalStatus Report).

The largest fraction of renewables is traditional biomass, whichcontributes around 9% of the total energy consumption. To convertbiomass to a more useful energy form, there are three main thermalprocesses available, namely pyrolysis, gasification and combustion(Bridgwater, A. V., Renewable fuels and chemicals by thermal processingof biomass. Chem. Eng. J. 2003, 91(2), 87-102). The main product fromthe pyrolysis of biomass is bio-oil. Bio-oil has problems of thermalinstability, affinity for water, corrosivity, high viscosity, and lowheating values due to its high oxygen content (Raymundo, L. M., et al.,Deoxygenation of Biomass Pyrolysis Vapors via in Situ and ex SituThermal and Biochar Promoted Upgrading. Energy Fuels 2019, 33 (3),2197-2207).

To expand the utility of the bio-oil, selective deoxygenation can beapplied to reduce oxygen from the compounds. Furthermore, recentadvances in biomass processing and lignin depolymerization have led to agreatly increased need for catalysts capable of selective deoxygenationof aromatic alcohols (Rahimi, A. et al., Nature 2014, 515, 249; Huang,X., et al., ACS Catal. 2015, 5 (12), 7359-7370; Gasser, C. A., et al.,Appl. Microbiol. Biotechnol. 2017, 101 (6), 2575-2588; Partenheimer, W.,Adv. Synth. Catal. 2009, 351 (3), 456-466.; Renders, T., et al., EnergyEnviron. Sci. 2017, 10 (7), 1551-1557; Das, A., et al., ACS SustainableChemistry & Engineering 2018, 6 (3), 3367-3374).

Deoxygenation of the aromatic alcohols would increase the energy densityof the resulting liquid fuel (Gollakota, A. R. K., et al., Renewable andSustainable Energy Reviews 2016, 58 (C), 1543-1568) and/or lead to theisolation of important industrial chemical feedstocks (Luo, H., et al.,Green Chem. 2018, 20 (3), 745-753). Selectively deoxygenating ligninderived compounds without hydrogenation of the aromatic units is ofspecific interest because aromatics and alkenes are higher valuechemicals compared to alkanes, hydrogen use efficiency would bemaximized, and carbon loss would be minimized (Nolte, M. W., et al.,Energy Technology 2017, 5 (1), 7-18).

Traditional nanoparticle based heterogeneous catalysts can achieveupwards of 80-90% selectivity for the hydrodeoxygenation of modelcompounds (Zakzeski, J., et al., Chem. Rev. 2010, 110 (6), 3552-3599;Shao, Y.; et al., Nat. Commun. 2017, 8 (1), 16104; Guo, T.; et al.,Applied Catalysis A: General 2017, 547, 30-36; Baddour, F. G.; et al.,ACS Sustainable Chemistry & Engineering 2017, 5 (12), 11433-11439; Hsu,P.-J.; et al., ACS Sustainable Chemistry & Engineering 2018, 6 (1),660-667; Ju, C.; et al., Green Chem. 2018, 20 (19), 4492-4499; Song, W.;et al., ACS Catal. 2019, 9 (1), 259-268). Of these model compounds,vanillyl alcohol has been previously studied as a commonly derivedchemical from lignin depolymerization. Heterogeneous Pd nanoparticlecatalysts have exhibited good product selectivity for the formation ofcreosol depending on the reaction additives as shown in Scheme 1 below(Hao, P.; et al., ACS Catal. 2018, 8 (12), 11165-11173; Lien, C.-H., etal., The Journal of Physical Chemistry C 2014, 118 (41), 23783-23789;Parsell, T. H.; et al., Chem. Sci. 2013, 4 (2), 806-813):

Molecular catalysts have also been examined for catalytichydrodeoxygenation (HDO) of benzylic alcohols due to the fact thatmolecular catalysts lack extended metallic surfaces and thus can avoidunwanted ring hydrogenation products (Liu, H.; et al., Science 2009,326, 1250-1252). A molecular palladium catalyst in homogeneous methanolsolution has exhibited complete selectivity for HDO over ringhydrogenation for benzylic substrates (DeLucia, N. A.; et al., Catal.Today 2018, 302, 146-150), and a molecular catalyst attached to thesurface of oxide particles has exhibited high selectivity and activitytowards the formation of cresol from vanillyl alcohol and vanillin(DeLucia, N. A., et al., ACS Catal. 2019, 9060-9071).

Given the importance of producing highly efficient bio-oils, new methodsand new catalysts with improved selectivity, activity, and durabilityare needed. Also are needed new methods and catalysts for efficient andselective hydrodeoxygenation of aromatic molecules. These needs andother needs are at least partially satisfied by the present disclosure.

SUMMARY

In accordance with the purposes of the disclosed materials and methods,as embodied and broadly described herein, the disclosed subject matter,in one aspect, relates to compounds, compositions and methods of makingand using compounds and compositions.

In some aspects, disclosed herein is a method comprising: selectivelydeoxygenating at least one oxygenated aromatic compound in the presenceof a hydrogen gas and a catalyst system to form a reaction product,wherein the catalyst system comprises a catalyst of formula (I):

-   wherein,-   R¹ is hydrogen, OH, O⁻, halogen, amine, C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy,    C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl,    C₆-C₁₄ aryloxy, C₃-C₁₀ cycloalkyl, or C₃-C₁₀ cycloalkenyl, wherein    R¹ is optionally substituted with C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy,    C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl,    aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy,    ketone, nitro, cyano, silyl, sulfo-oxo, sulfonyl, sulfone,    sulfoxide, thiol, or phosphonyl;-   each R² is, independent of the other, C₁-C₁₀ alkyl, C₂-C₁₀ alkenyl,    C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃ heteroaryl, wherein R² is    optionally substituted with C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀    alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde,    amino, carboxylic acid, ester, ether, halide, hydroxy, ketone,    nitro, cyano, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or    thiol;-   each R³ and R⁴ are, independent of the other, hydrogen, C₁-C₁₀    alkyl, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃    heteroaryl, wherein R³ and R⁴ are optionally substituted with C₁-C₁₀    alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl,    C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic acid, ester, ether,    halide, hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo, sulfonyl,    sulfone, sulfoxide, or thiol, or R³ and R⁴ combine together with the    atoms to which they are attached to form a cycloalkyl,    cycloheteroaryl, aryl, or heteroaryl;-   each R¹⁶ and R¹⁷ are, independent of the other, hydrogen, OH, O⁻,    halogen, amine, C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀    alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, C₆-C₁₄ aryloxy, C₃-C₁₀    cycloalkyl, or C₃-C₁₀ cycloalkenyl, wherein each R¹⁶ and R¹⁵,    independent of the other, is optionally substituted with C₁-C₁₀    alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl,    C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic acid, ester, ether,    halide, hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo, sulfonyl,    sulfone, sulfoxide, thiol, phosphonyl-   M is Ru or Ir;-   each L is independently selected from Cl, Br, CH₃CN, DMF, H₂O,    bipyridine, phenylpyridine, CO₂, and a CNC-pincer ligand; and-   n is 1, 2, or 3.

Still, in further aspects, the aromatic compound having at least onehydroxyl group of the disclosed methods has a formula (II):

wherein,

-   R⁵ is independently selected from hydrogen, substituted or    unsubstituted C₁-C₆-alkyl; R¹¹—OH, —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,    substituted or unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls,    C₂-C₁₀ alkenyl, and Ar′;-   R⁶ is independently selected from hydrogen, hydrogen, substituted or    unsubstituted R¹¹—OH; —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹, substituted or    unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl,    and Ar′;-   R⁷ is independently selected from hydrogen, substituted or    unsubstituted C₁-C₆-alkyl, R¹¹—OH, —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,    substituted or unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls,    C₂-C₁₀ alkenyl, and Ar′;-   R⁸ is independently selected from hydrogen, substituted or    unsubstituted C₁-C₆-alkyl, R¹¹—OH; —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,    substituted or unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls,    C₂-C₁₀ alkenyl, and Ar′;-   R⁹ is independently selected from hydrogen, substituted or    unsubstituted C₁-C₆-alkyl, R¹¹—OH; —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,    substituted or unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls,    C₂-C₁₀ alkenyl, and Ar′;-   R¹⁰ is independently selected from hydrogen, substituted or    unsubstituted C₁-C₆-alkyl; R¹¹—OH; —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,    substituted or unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls,    C₂-C₁₀ alkenyl, and Ar′;-   wherein when R⁶, R⁷, R⁹, and R¹⁰ are all hydrogen, R⁵ is R¹¹—OH,    R¹⁸OR¹⁹, or R²⁰COR²¹,-   wherein R¹¹ is a bond, substituted or unsubstituted C₁-C₆ alkyl,    C₂-C₁₀ alkenyl, or Ar″;-   R¹² is independently selected from hydrogen, substituted or    unsubstituted C₁-C₆ alkyl, C₂-C₁₀ alkenyl, and Ar″,-   R¹⁸ is independently selected from substituted or unsubstituted    C₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀ cycloalkyls and    heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;-   R¹⁹ is independently selected from substituted or unsubstituted    C₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀ cycloalkyls and    heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;-   R²⁰ is independently selected from a bond, substituted or    unsubstituted C₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀    cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;-   R²¹ is independently selected from hydrogen, hydroxyl, C₁-C₁₀ alkyl,    C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃    heteroaryl, C₆-C₁₄ aryloxy, C₃-C₁₀ cycloalkyl, or C₃-C₁₀    cycloalkenyl and Ar′, wherein R²¹ is optionally substituted with    C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄    aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic acid, ester,    ether, halide, hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo,    sulfonyl, sulfone, sulfoxide, thiol, phosphonyl;-   Ar′ is a C₆-C₁₄ aryl or heteroaryl group optionally substituted with    1, 2, or 3 optional substituents; and-   Ar″ is a C₆-C₁₄ aryl or heteroaryl group optionally substituted with    1, 2, or 3 optional substituents;-   Ar′″ is a C₆-C₁₄ aryl or heteroaryl group optionally substituted    with 1, 2, or 3 optional substituents;    wherein Ar′, Ar″, or Ar′″, are the same or different.

In still further aspects, the reaction product formed according to thedisclosed methods comprises a compound A of formula (III)

wherein R¹³ is R¹¹—H.

In yet according to other aspects of the disclosure, the reactionproduct formed according to the disclosed methods can also comprise acompound B of formula (IV):

wherein R¹⁴ is —OR¹⁵, wherein R₁₅ is a C₁-C₁₀ alkyl group.

In still further aspects and as disclosed herein, the compound A isselectively formed over the compound B.

Also disclosed herein is a catalyst of formula (I):

-   -   wherein,    -   R¹ is hydrogen, OH, O⁻, halogen, amine, C₁-C₁₀ alkyl, C₁-C₁₀        alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃        heteroaryl, C₆-C₁₄ aryloxy, C₃-C₁₀ cycloalkyl, or C₃-C₁₀        cycloalkenyl, wherein R¹ is optionally substituted with C₁-C₁₀        alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄        aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic acid,        ester, ether, halide, hydroxy, ketone, nitro, cyano, silyl,        sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol, or phosphonyl;    -   each R² is, independent of the other, C₁-C₁₀ alkyl, C₂-C₁₀        alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃ heteroaryl,        wherein R² is optionally substituted with C₁-C₁₀ alkyl, C₁-C₁₀        alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃        heteroaryl, aldehyde, amino, carboxylic acid, ester, ether,        halide, hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo,        sulfonyl, sulfone, sulfoxide, or thiol;    -   each R³ and R⁴ are, independent of the other, hydrogen, C₁-C₁₀        alkyl, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃        heteroaryl, wherein R³ and R⁴ are optionally substituted with        C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl,        C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic        acid, ester, ether, halide, hydroxy, ketone, nitro, cyano,        silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol, or R³        and R⁴ combine together with the atoms to which they are        attached to form a cycloalkyl, cycloheteroaryl, aryl, or        heteroaryl;    -   each R¹⁶ and R¹⁷ are, independent of the other, hydrogen, OH,        O⁻, halogen, amine, C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl,        C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, C₆-C₁₄ aryloxy,        C₃-C₁₀ cycloalkyl, or C₃-C₁₀ cycloalkenyl, wherein each R¹⁶ and        R₁₅, independent of the other, is optionally substituted with        C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl,        C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic        acid, ester, ether, halide, hydroxy, ketone, nitro, cyano,        silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol,        phosphonyl;    -   M is Ru or Ir;    -   each L is independently selected from Cl, Br, CH₃CN, DMF, H₂O,        bipyridine, phenylpyridine, CO₂, and a CNC-pincer ligand; and    -   n is 1, 2, or 3.

Additional advantages will be set forth, in part, in the detailedfigures and claims which follow, and in part will be derived from thedetailed description, or can be learned by practice of the invention.The advantages described below will be realized and attained by means ofthe elements and combinations particularly pointed out in the appendedclaims. It is to be understood that both the foregoing generaldescription and the following detailed description are exemplary andexplanatory only and are not restrictive.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 depicts molecular diagrams of complexes 9, 10, 11 (same as1^(NMe2)) 12, 13e, and 13 (same as 1^(OH)) based on crystallographicdata with hydrogen atoms (except for H-bonded one in 13 (same as1^(OH))) and counter-anions removed for clarity. Thermal ellipsoids aredrawn at the 40% probability level.

FIG. 2 depicts a Beer's law and normalized absorption spectra inacetonitrile for compounds 9, 10, 11 (same as 1^(Nme2)), 12, and 13(same as 1^(OH)).

The accompanying figures, which are incorporated in and constitute apart of this specification, illustrate several aspects described below.

DETAILED DESCRIPTION

The materials, compounds, compositions, and methods described herein maybe understood more readily by reference to the following detaileddescription of specific aspects of the disclosed subject matter, theFigures, and the Examples included therein.

Before the present materials, compounds, compositions, and methods aredisclosed and described, it is to be understood that the aspectsdescribed below are not limited to specific synthetic methods orspecific reagents, as such may, of course, vary. It is also to beunderstood that the terminology used herein is for the purpose ofdescribing particular aspects only and is not intended to be limiting.

Also, throughout this specification, various publications arereferenced. The disclosures of these publications in their entiretiesare hereby incorporated by reference into this application in order tomore fully describe the state of the art to which the disclosed matterpertains. The references disclosed are also individually andspecifically incorporated by reference herein for the material containedin them that is discussed in the sentence in which the reference isrelied upon.

Definitions

As used herein, the terms “optional” or “optionally” means that thesubsequently described event or circumstance can or cannot occur andthat the description includes instances where said event or circumstanceoccurs and instances where it does not.

It is appreciated that certain features of the disclosure, which are,for clarity, described in the context of separate aspects, can also beprovided in combination in a single aspect, Conversely, various featuresof the disclosure, which are, for brevity, described in the context of asingle aspect, can also be provided separately or in any suitablesubcombination.

As used in the description and the appended claims, the singular forms“a,” “an,” and “the” include plural referents unless the context clearlydictates otherwise. Thus, for example, reference to “a composition”includes mixtures of two or more such compositions, reference to “anagent” includes mixtures of two or more such agents and the like.

It is also to be understood that the terminology used herein is for thepurpose of describing particular aspects only and is not intended to belimiting. As used in the specification and the claims, the term“comprising” can include the aspects “consisting of” and “consistingessentially of.”

For the terms “for example” and “such as,” and grammatical equivalencesthereof, the phrase “and without limitation” is understood to followunless explicitly stated otherwise.

As used herein, the term “substituted” means that a hydrogen atom isremoved and replaced by a substituent. It is contemplated to include allpermissible substituents of organic compounds. As used herein, thephrase “optionally substituted” means unsubstituted or substituted. Itis to be understood that substitution at a given atom is limited byvalency. In a broad aspect, the permissible substituents include acyclicand cyclic, branched and unbranched, carbocyclic and heterocyclic, andaromatic and nonaromatic substituents of organic compounds. Illustrativesubstituents include, for example, those described below. Thepermissible substituents can be one or more and the same or differentfor appropriate organic compounds. For purposes of this disclosure, theheteroatoms, such as nitrogen, can have hydrogen substituents and/or anypermissible substituents of organic compounds described herein whichsatisfy the valencies of the heteroatoms. This disclosure is notintended to be limited in any manner by the permissible substituents oforganic compounds. Also, the terms “substitution” or “substituted with”include the implicit proviso that such substitution is in accordancewith a permitted valence of the substituted atom and the substituent andthat the substitution results in a stable compound, e.g., a compoundthat does not spontaneously undergo transformation such as byrearrangement, cyclization, elimination, etc. In still further aspects,it is understood that when the disclosure describes a group beingsubstituted, it means that the group is substituted with one or more(i.e., 1, 2, 3, 4, or 5) groups as allowed by valence selected fromalkyl, halogenated alkyl, alkoxy, alkenyl, alkynyl, aryl, heteroaryl,aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone,nitro, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol, asdescribed below.

The term “compound,” as used herein, is meant to include allstereoisomers, geometric isomers, tautomers, and isotopes of thestructures depicted. Compounds described herein identified by name orstructure as one particular tautomeric form are intended to includeother tautomeric forms unless otherwise specified.

All compounds, and salts thereof (e.g., pharmaceutically acceptablesalts), can be found together with other substances such as water andsolvents (e.g., hydrates and solvates).

Compounds provided herein also can include tautomeric forms. Tautomericforms result from the swapping of a single bond with an adjacent doublebond together with the concomitant migration of a proton. Tautomericforms include prototropic tautomers that are isomeric protonation stateshaving the same empirical formula and total charge. Example prototropictautomers include ketone-enol pairs, amide-imidic acid pairs, lactamlactim pairs, enamine-imine pairs, and annular forms where a proton canoccupy two or more positions of a heterocyclic system, for example, 1H-and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H-isoindole,and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium orsterically locked into one form by appropriate substitution.

Compounds provided herein can also include all isotopes of atomsoccurring in the intermediates or final compounds. Isotopes includethose atoms having the same atomic number but different mass numbers.For example, isotopes of hydrogen include hydrogen, tritium, anddeuterium.

Also provided herein are salts of the compounds described herein. It isunderstood that the disclosed salts can refer to derivatives of thedisclosed compounds wherein the parent compound is modified byconverting an existing acid or base moiety to its salt form. Examples ofthe salts include, but are not limited to, mineral or organic acid saltsof basic residues such as amines; alkali or organic salts of acidicresidues such as carboxylic acids; and the like. The salts of thecompounds provided herein include the conventional non-toxic salts ofthe parent compound formed, for example, from non-toxic inorganic ororganic acids. The salts of the compounds provided herein can besynthesized from the parent compound that contains a basic or acidicmoiety by conventional chemical methods. Generally, such salts can beprepared by reacting the free acid or base forms of these compounds witha stoichiometric amount of the appropriate base or acid in water or inan organic solvent, or in a mixture of the two. In various aspects, anonaqueous media like ether, ethyl acetate, alcohols (e.g., methanol,ethanol, isopropanol, or butanol) or acetonitrile (ACN) can be used.Lists of suitable salts are found in Remingtons's PharmaceuticalSciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418and Journal of Pharmaceutical Science, 66, 2 (1977). Conventionalmethods for preparing salt forms are described, for example, in Handbookof Pharmaceutical Salts: Properties, Selection, and Use, Wiley-VCH,2002.

In various aspects, the compounds provided herein, or salts thereof, aresubstantially isolated. By “substantially isolated” is meant that thecompound is at least partially or substantially separated from theenvironment in which it was formed or detected. Partial separation caninclude, for example, a composition enriched in the compounds providedherein. Substantial separation can include compositions containing atleast about 50%, at least about 60%, at least about 70%, at least about80%, at least about 90%, at least about 95%, at least about 97%, or atleast about 99% by weight of the compounds provided herein, or saltthereof. Methods for isolating compounds and their salts are routine inthe art. As used herein, chemical structures that contain one or morestereocenters depicted with dashed and bold bonds (i.e.,) are meant toindicate absolute stereochemistry of the stereocenter(s) present in thechemical structure. As used herein, bonds symbolized by a simple line donot indicate a stereo-preference. Unless otherwise indicated to thecontrary, chemical structures, which include one or more stereocenters,illustrated herein without indicating absolute or relativestereochemistry encompass all possible stereoisomeric forms of thecompound (e.g., diastereomers and enantiomers) and mixtures thereof.Structures with a single bold or dashed line and at least one additionalsimple line encompass a single enantiomeric series of all possiblediastereomers.

The resolution of racemic mixtures of compounds can be carried out usingappropriate methods. An exemplary method includes fractionalrecrystallization using a chiral resolving acid that is an opticallyactive, salt-forming organic acid. Suitable resolving agents forfractional recrystallization methods are, for example, optically activeacids, such as the D and L forms of tartaric acid, diacetyltartaricacid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, orthe various optically active camphorsulfonic acids such ascamphorsulfonic acid. Other resolving agents suitable for fractionalcrystallization methods include stereoisomerically pure forms ofmethylbenzylamine (e.g., S and R forms, or diastereomerically pureforms), 2-phenylglycinol, norephedrine, ephedrine, N-methylephedrine,cyclohexylamine, 1,2-diaminocyclohexane, and the like.

Resolution of racemic mixtures can also be carried out by elution on acolumn packed with an optically active resolving agent (e.g.,dinitrobenzoylphenylglycine). Suitable elution solvent compositions canbe determined by one skilled in the art.

The expressions “ambient temperature” and “room temperature” as usedherein are understood in the art and refer generally to a temperature,e.g., a reaction temperature, that is about the temperature of the roomin which the reaction is carried out, for example, a temperature fromabout 20° C. to about 30° C.

“R¹,” “R²,” “R³,” “R⁴,” etc. are used herein as generic symbols torepresent various specific substituents. These symbols can be anysubstituent, not limited to those disclosed herein, and when they aredefined to be certain substituents in one instance, they can, in anotherinstance, be defined as some other substituents.

At various places in the present specification, divalent linkingsubstituents are described. It is specifically intended that eachdivalent linking substituent includes both the forward and backwardforms of the linking substituent. For example, —NR(CR′R″)_(n)-includesboth —NR(CR′R″)_(n)— and —(CR′R″)_(n)NR—. Where the structure clearlyrequires a linking group, the Markush variables listed for that groupare understood to be linking groups.

The term “n-membered” where n is an integer typically describes thenumber of ring-forming atoms in a moiety where the number ofring-forming atoms is n. For example, piperidinyl is an example of a6-membered heterocycloalkyl ring, pyrazolyl is an example of a5-membered heteroaryl ring, pyridyl is an example of a 6-memberedheteroaryl ring, and 1,2,3,4-tetrahydro-naphthalene is an example of a10-membered cycloalkyl group.

Throughout the definitions, the term “C_(n)-C_(m)” indicates a rangethat includes the endpoints, wherein n and m are integers and indicatethe number of carbons. Examples include, without limitation, C₁-C₄,C₁-C₆, and the like.

The term “aliphatic” as used herein refers to a non-aromatic hydrocarbongroup and includes branched and unbranched, alkyl, alkenyl, or alkynylgroups. As used herein, the term “C_(n)-C_(m) alkyl,” employed alone orin combination with other terms, refers to a saturated hydrocarbon groupthat may be straight-chain or branched, having n to m carbons. Examplesof alkyl moieties include, but are not limited to, chemical groups suchas methyl, ethyl, n-propyl, isopropyl, n-butyl, teri-butyl, isobutyl,sec-butyl; higher homologs such as 2-methyl-l-butyl, n-pentyl, 3-pentyl,n-hexyl, 1,2,2-trimethylpropyl, heptyl, octyl, nonyl, decyl, dodecyl,tetradecyl, hexadecyl, eicosyl, tetracosyl, and the like. In variousaspects, the alkyl group contains from 1 to 24 carbon atoms, from 1 to12 carbon atoms, from 1 to 10 carbon atoms, from 1 to 8 carbon atoms,from 1 to 6 carbon atoms, from 1 to 4 carbon atoms, from 1 to 3 carbonatoms, or 1 to 2 carbon atoms. The alkyl group can also be substitutedor unsubstituted. Throughout the specification, “alkyl” is generallyused to refer to both unsubstituted alkyl groups and substituted alkylgroups; however, substituted alkyl groups are also specifically referredto herein by identifying the specific substituent(s) on the alkyl group.The alkyl group can be substituted with one or more groups including,but not limited to, alkyl, halogenated alkyl, alkoxy, alkenyl, alkynyl,aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether,halide, hydroxy, ketone, nitro, silyl, sulfo-oxo, sulfonyl, sulfone,sulfoxide, or thiol, as described below.

For example, the term “halogenated alkyl” specifically refers to analkyl group that is substituted with one or more halide, e.g., fluorine,chlorine, bromine, or iodine. The term “alkoxyalkyl” specifically refersto an alkyl group that is substituted with one or more alkoxy groups, asdescribed below. The term “alkylamino” specifically refers to an alkylgroup that is substituted with one or more amino groups, as describedbelow and the like. When “alkyl” is used in one instance, and a specificterm such as “alkylalcohol” is used in another, it is not meant to implythat the term “alkyl” does not also refer to specific terms such as“alkylalcohol” and the like.

As used herein, “C_(n)-C_(m) alkenyl” refers to an alkyl group havingone or more double carbon-carbon bonds and having n to m carbons,Example alkenyl groups include, but are not limited to, ethenyl,n-propenyl, isopropenyl, n-butenyl, seobutenyl, and the like. In variousaspects, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbonatoms. Asymmetric structures such as (R¹R²)C═C(R³R⁴) are intended toinclude both the E and Z isomers. This can be presumed in structuralformulae herein wherein an asymmetric alkene is present, or it can beexplicitly indicated by the bond symbol C═C. The alkenyl group can besubstituted with one or more groups including, but not limited to,alkyl, halogenated alkyl, alkoxy, alkenyl, alkynyl, aryl, heteroaryl,aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone,nitro, cyano, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol,thiol, or phosphonyl, as described below.

As used herein, “C_(n)-C_(m) alkynyl” refers to an alkyl group havingone or more triple carbon-carbon bonds and having n to m carbons.Exemplary alkynyl groups include, but are not limited to, ethynyl,propyn-1-yl, propyn-2-yl, and the like. In various aspects, the alkynylmoiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms. The alkynylgroup can be substituted with one or more groups including, but notlimited to, alkyl, halogenated alkyl, alkoxy, alkenyl, alkynyl, aryl,heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide,hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo, sulfonyl, sulfone,sulfoxide, thiol, or phosphonyl, as described below

As used herein, the term “C_(n)-C_(m) alkylene,” employed alone or incombination with other terms, refers to a divalent alkyl linking grouphaving n to m carbons. Examples of alkylene groups include, but are notlimited to, ethan-1,2-diyl, propan-1,3-diyl, propan-1,2-diyl,butan-1,4-diyl, butan-1,3-diyl, butan-1,2-diyl,2-methyl-propan-1,3-diyl, and the like. In various aspects, the alkylenemoiety contains 2 to 6, 2 to 4, 2 to 3, 1 to 6, 1 to 4, or 1 to 2 carbonatoms.

As used herein, the term “C_(n)-C_(m) alkoxy,” employed alone or incombination with other terms, refers to a group of formula —O-alkyl,wherein the alkyl group has n to m carbons. Examples of alkoxy groupsinclude methoxy, ethoxy, propoxy (e.g., w-propoxy and isopropoxy),ten-butoxy, and the like. In various aspects, the alkyl group has 1 to6, 1 to 4, or 1 to 3 carbon atoms.

The terms “amine” or “amino” as used herein are represented by theformula —NR¹R², where R¹ and R² can each be substitution group asdescribed herein, such as hydrogen, an alkyl, halogenated alkyl,alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl,heterocycloalkyl, or heterocycloalkenyl group described above. “Amido”is —C(O)NR¹R².

As used herein, the term “C_(n)-C_(m) alkylamino” refers to a group offormula —NH(alkyl), wherein the alkyl group has n to m carbon atoms. Invarious aspects, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbonatoms.

As used herein, the term “C_(n)-C_(m) alkoxycarbonyl” refers to a groupof formula —C(O)O-alkyl, wherein the alkyl group has n to m carbonatoms. In various aspects, the alkyl group has 1 to 6, 1 to 4, or 1 to 3carbon atoms.

As used herein, the term “C_(n)-C_(m) alkylcarbonyl” refers to a groupof formula —C(O)-alkyl, wherein the alkyl croup has n to m carbon atoms.In various aspects, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbonatoms.

As used herein, the term “C_(n)-C_(m) alkylcarbonylamino” refers to agroup of formula —NHC(O)-alkyl, wherein the alkyl group has n to mcarbon atoms. In various aspects, the alkyl group has 1 to 6, 1 to 4, or1 to 3 carbon atoms.

As used herein, the term “C_(n)-C_(m) alkylsulfonylamino” refers to agroup of formula —NHS(O)₂-alkyl, wherein the alkyl group has n to mcarbon atoms. In various aspects, the alkyl group has 1 to 6, 1 to 4, or1 to 3 carbon atoms.

The term “aldehyde,” as used herein, is represented by the formula—C(O)H. Throughout this specification, “C(O)” or “CO” is a shorthandnotation for C═O, which is also referred to herein as a “carbonyl.”

The term “carboxylic acid,” as used herein, is represented by theformula —C(O)OH. A “carboxylate” or “carboxyl” group as used herein isrepresented by the formula —C(O)O⁻.

The term “ester” as used herein is represented by the formula —OC(O)R¹or —C(O)OR¹, where R¹ can be an alkyl, halogenated alkyl, alkenyl,alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl,or heterocycloalkenyl group described above.

The term “ether” as used herein is represented by the formula R¹OR²,where R¹ and R² can be, independently, an alkyl, halogenated alkyl,alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl,heterocycloalkyl, or heterocycloalkenyl group described above.

The term “ketone” as used herein is represented by the formula R¹C(O)R²,where R¹ and R² can be, independently, an alkyl, halogenated alkyl,alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl,heterocycloalkyl, or heterocycloalkenyl group described above.

As used herein, the term “aminosulfonyl” refers to a group of formula—S(O)₂NH₂.

As used herein, the term “C_(n)-C_(m) alkylaminosulfonyl” refers to agroup of formula —S(O)₂NH(alkyl), wherein the alkyl group has n to mcarbon atoms. In various aspects, the alkyl group has 1 to 6, 1 to 4, or1 to 3 carbon atoms.

As used herein, the term “di(C_(n)-C_(m) alkyl)aminosulfonyl” refers toa group of formula —S(O)₂N(alkyl)₂, wherein each alkyl groupindependently has n to m carbon atoms. In various aspects, each alkylgroup has, independently, 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

As used herein, the term “aminosulfonylamino” refers to a group offormula —NHS(O)₂NH₂.

As used herein, the term “C_(n)-C_(m) alkylaminosulfonylamino” refers toa group of formula —NHS(O)₂NH(alkyl), wherein the alkyl group has n to mcarbon atoms. In various aspects, the alkyl group has 1 to 6, 1 to 4, or1 to 3 carbon atoms.

As used herein, the term “di(C_(n)-C_(m) alkyl)aminosulfonylamino”refers to a group of formula —NHS(O)₂N(alkyl)₂, wherein each alkyl groupindependently has n to m carbon atoms. In various aspects, each alkylgroup has, independently, 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

As used herein, the term “aminocarbonylamino,” employed alone or incombination with other terms, refers to a group of formula —NHC(O)NH₂.

As used herein, the term “C_(n)-C_(m) alkylaminocarbonylamino” refers toa group of formula —NHC(O)NH(alkyl), wherein the alkyl group has n tomcarbon atoms. In various aspects, the alkyl group has 1 to 6, 1 to 4, or1 to 3 carbon atoms.

As used herein, the term “di(C_(n)-C_(m) alkyl)aminocarbonylamino”refers to a group of formula —NHC(O)N(alkyl)₂, wherein each alkyl groupindependently has n to m carbon atoms. In various aspects, each alkylgroup has, independently, 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

As used herein, the term “C_(n)-C_(m) alkylcarbamyl” refers to a groupof formula —C(O)—NH(alkyl), wherein the alkyl group has n to m carbonatoms. In various aspects, the alkyl group has 1 to 6, 1 to 4, or 1 to 3carbon atoms.

As used herein, the term “thio” refers to a group of formula —SH.

As used herein, the term “C_(n)-C_(m) alkylthio” refers to a group offormula —S— alkyl, wherein the alkyl group has n to m carbon atoms. Invarious aspects, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbonatoms.

As used herein, the term “C_(n)-C_(m) alkylsulfinyl” refers to a groupof formula —S(O)-alkyl, wherein the alkyl group has n to m carbon atoms.In various aspects, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbonatoms.

As used herein, the term “C_(n)-C_(m) alkylsulfonyl” refers to a groupof formula —S(O)₂-alkyl, wherein the alkyl group has n to m carbonatoms. In various aspects, the alkyl group has 1 to 6, 1 to 4, or 1 to 3carbon atoms.

As used herein, the term “carbamyl” to a group of formula —C(O)NH₂.

As used herein, the term “carbonyl” employed alone or in combinationwith other terms, refers to a —C(═O)— group, which may also be writtenas C(O).

As used herein, the term “carboxy” refers to a group of formula —C(O)OH.

As used herein, the term “(C_(n)-C_(m))(C_(n)-C_(m))amino” refers to agroup of formula —N(alkyl)₂, wherein the two alkyl groups each has,independently, n to m carbon atoms. In various aspects, each alkyl groupindependently has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

As used herein, the term “di(C_(n)-C_(m)-alkyl)carbamyl” refers to agroup of formula —C(O)N(alkyl)₂, wherein the two alkyl groups each has,independently, n to m carbon atoms. In various aspects, each alkyl groupindependently has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

As used herein, “halogen” refers to F, Cl, Br, or I.

The term “hydroxyl” as used herein is represented by the formula —OH.

The term “cyano” as used herein is represented by the formula —CN.

The term “nitro” as used herein is represented by the formula —NO₂.

The term “phosphonyl” is used herein to refer to the phospho-oxo grouprepresented by the formula —P(O)(OR¹)₂, where R¹ can be absent,hydrogen, an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, orcycloalkenyl.

The term “silyl” as used herein is represented by the formula —SiR¹R²R³,where R¹, R², and R³ can be, independently, hydrogen, alkyl, halogenatedalkyl, alkoxy, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl,cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group describedabove.

The term “sulfonyl” is used herein to refer to the sulfo-oxo grouprepresented by the formula —S(O)₂R¹, where R¹ can be hydrogen, an alkyl,halogenated alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl,cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group describedabove.

The term “sulfonylamino” or “sulfonamide” as used herein is representedby the formula —S(O)₂NH—.

As used herein, “C_(n)-C_(m) haloalkoxy” refers to a group of formula—O-haloalkyl having n to m carbon atoms. An example haloalkoxy group isOCF₃. In various aspects, the haloalkoxy group is fluorinated only. Invarious aspects, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbonatoms.

As used herein, the term “C_(n)-C_(m) haloalkyl,” employed alone or incombination with other terms, refers to an alkyl group having from onehalogen atom to 2s+l halogen atoms which may be the same or different,where “s” is the number of carbon atoms in the alkyl group, wherein thealkyl group has n to m carbon atoms. In various aspects, the haloalkylgroup is fluorinated only. In various aspects, the alkyl group has 1 to6, 1 to 4, or 1 to 3 carbon atoms.

As used herein, the term “amine base” refers to a mono-substituted aminogroup (i.e., primary amine base), di-substituted amino group (i.e.,secondary amine base), or a tri-substituted amine group (i.e., tertiaryamine base). Exemplary mono-substituted amine bases include methylamine,ethylamine, propylamine, butylamine, and the like. Exampledi-substituted amine bases include dimethylamine, diethylamine,dipropylamine, dibutylamine, pyrrolidine, piperidine, azepane,morpholine, and the like. In various aspects, the tertiary amine has theformula N(R′)₃, wherein each R′ is independently C₁-6 alkyl, 3-10 membercycloalkyl, 4-10 membered heterocycloalkyl, 1-10 membered heteroaryl,and 5-10 membered aryl, wherein the 3-10 member cycloalkyl, 4-10membered heterocycloalkyl, 1-10 membered heteroaryl, and 5-10 memberedaryl is optionally substituted by 1, 2, 3, 4, 5, or 6 Ci-6 alkyl groups.Exemplary tertiary amine bases include trimethylamine, triethylamine,tripropylamine, triisopropylamine, tributylamine, tri-tert-butylamine,N,N-dimethylethanamine, N-ethyl-N-methylpropan-2-amine,N-ethyl-N-isopropylpropan-2-amine, morpholine, N-methylmorpholine, andthe like. In various aspects, the term “tertiary amine base” refers to agroup of formula N(R)₃, wherein each R is independently a linear orbranched C₁-6 alkyl group.

As used herein, “cycloalkyl” refers to non-aromatic cyclic hydrocarbonsincluding cyclized alkyl and/or alkenyl groups. Cycloalkyl groups caninclude mono- or polycyclic (e.g., having 2, 3 or 4 fused rings) groupsand spirocycles. Cycloalkyl groups can have 3, 4, 5, 6, 7, 8, 9, or 10ring-forming carbons (C₃₋₁₀). Ring-forming carbon atoms of a cycloalkylgroup can be optionally substituted by oxo or sulfido (e.g., C(O) orC(S)). Cycloalkyl groups also include cycloalkylidenes. Examples ofcycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl,cycloheptatrienyl, norbornyl, norpinyl, norcarnyl, and the like. Invarious aspects, cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cyclopentyl, or adamantyl. In various aspects, thecycloalkyl has 6-10 ring-forming carbon atoms. In various aspects,cycloalkyl is cyclohexyl or adamantyl. Also included in the definitionof cycloalkyl are moieties that have one or more aromatic rings fused(i.e., having a bond in common with) to the cycloalkyl ring, forexample, benzo or thienyl derivatives of cyclopentane, cyclohexane, andthe like. A cycloalkyl group containing a fused aromatic ring can beattached through any ring-forming atom, including a ring-forming atom ofthe fused aromatic ring.

As used herein, “heterocycloalkyl” refers to non-aromatic monocyclic orpolycyclic heterocycles having one or more ring-forming heteroatomsselected from O, N, or S. Included in heterocycloalkyl are monocyclic4-, 5-, 6-, and 7-membered heterocycloalkyl groups. Heterocycloalkylgroups can also include spirocycles. Examples of heterocycloalkyl groupsinclude pyrrolidin-2-one, 1,3-isoxazolidin-2-one, pyranyl,tetrahydropuran, oxetanyl, azetidinyl, morpholino, thiomorpholino,piperazinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl,pyrrolidinyl, isoxazolidinyl, isothiazolidinyl, pyrazolidinyl,oxazolidinyl, thiazolidinyl, imidazolidinyl, azepanyl, benzazapene, andthe like. Ring-forming carbon atoms and heteroatoms of aheterocycloalkyl group can be optionally substituted by oxo or sulfido(e.g., C(O), S(O), C(S), or S(O)₂, etc.). The heterocycloalkyl group canbe attached through a ring-forming carbon atom or a ring-formingheteroatom. In various aspects, the heterocycloalkyl group contains 0 to3 double bonds. In various aspects, the heterocycloalkyl group contains0 to 2 double bonds. Also included in the definition of heterocycloalkylare moieties that have one or more aromatic rings fused (i.e., having abond in common with) to the cycloalkyl ring, for example, benzo orthienyl derivatives of piperidine, morpholine, azepine, etc. Aheterocycloalkyl group containing a fused aromatic ring can be attachedthrough any ring-forming atom, including a ring-forming atom of thefused aromatic ring. In various aspects, the heterocycloalkyl has 4-10,4-7 or 4-6 ring atoms with 1 or 2 heteroatoms independently selectedfrom nitrogen, oxygen, or sulfur and having one or more oxidized ringmembers.

The term “cycloalkenyl,” as used herein, is a non-aromatic carbon-basedring composed of at least three carbon atoms and containing at least onedouble bond, i.e., C═C. Examples of cycloalkenyl groups include, but arenot limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl,cyclopentadienyl, cyclohexenyl, cyclohexadienyl, and the like. The term“heterocycloalkenyl” is a type of cycloalkenyl group as defined above,and is included within the meaning of the term “cycloalkenyl,” where atleast one of the carbon atoms of the ring is substituted with aheteroatom such as, but not limited to, nitrogen, oxygen, sulfur, orphosphorus. The cycloalkenyl group and heterocycloalkenyl group can besubstituted or unsubstituted. The cycloalkenyl group andheterocycloalkenyl group can be substituted with one or more groupsincluding, but not limited to, alkyl, alkoxy, alkenyl, alkynyl, aryl,heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide,hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo, sulfonyl, sulfone,sulfoxide, thiol, or phosphonyl, as described herein.

The term “cyclic group” is used herein to refer to either aryl groups,non-aryl groups (i.e., cycloalkyl, heterocycloalkyl, cycloalkenyl, andheterocycloalkenyl groups), or both. Cyclic groups have one or more ringsystems that can be substituted or unsubstituted. A cyclic group cancontain one or more aryl groups, one or more non-aryl groups, or one ormore aryl groups and one or more non-aryl groups.

As used herein, the term “aryl,” employed alone or in combination withother terms, refers to an aromatic hydrocarbon group, which may bemonocyclic or polycyclic (e.g., having 2, 3 or 4 fused rings). The term“C_(n-m) aryl” refers to an aryl group having from n to m ring carbonatoms. Aryl groups include, e.g., phenyl, naphthyl, anthracenyl,phenanthrenyl, indanyl, indenyl, and the like. In various aspects, arylgroups have from 6 to about 20 carbon atoms, from 6 to about 15 carbonatoms, or from 6 to about 10 carbon atoms. In various aspects, the arylgroup is a substituted or unsubstituted phenyl.

As used herein, “heteroaryl” refers to a monocyclic or polycyclicaromatic heterocycle having at least one heteroatom ring member selectedfrom sulfur, oxygen, phosphorus, and nitrogen. In various aspects, theheteroaryl ring has 1, 2, 3, or 4 heteroatom ring members independentlyselected from nitrogen, sulfur and oxygen. In various aspects, anyring-forming N in a heteroaryl moiety can be an N-oxide. In variousaspects, the heteroaryl has 5-10 ring atoms and 1, 2, 3 or 4 heteroatomring members independently selected from nitrogen, sulfur and oxygen. Invarious aspects, the heteroaryl has 5-6 ring atoms and 1 or 2 heteroatomring members independently selected from nitrogen, sulfur and oxygen. Invarious aspects, the heteroaryl is a five-membered or six-memberedheteroaryl ring. A five-membered heteroaryl ring is a heteroaryl with aring having five ring atoms wherein one or more (e.g., 1, 2, or 3) ringatoms are independently selected from N, O, and S. Exemplaryfive-membered ring heteroaryls are thienyl, furyl, pyrrolyl, imidazolyl,thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, isoxazolyl,1,2,3-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl,1,2,4-triazolyl, 1,2,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-triazolyl,1,3,4-thiadiazolyl, and 1,3,4-oxadiazolyl. A six-membered heteroarylring is a heteroaryl with a ring having six ring atoms wherein one ormore (e.g., 1, 2, or 3) ring atoms are independently selected from N, O,and S. Exemplary six-membered ring heteroaryls are pyridyl, pyrazinyl,pyrimidinyl, triazinyl, and pyridazinyl.

The aryl or heteroaryl group can be substituted with one or more groupsincluding, but not limited to, alkyl, halogenated alkyl, alkoxy,alkenyl, alkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid,ester, ether, halide, hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo,sulfonyl, sulfone, sulfoxide, thiol, or phosphonyl, as described herein.The term “biaryl” is a specific type of aryl group and is included inthe definition of aryl. Biaryl refers to two aryl groups that are boundtogether via a fused ring structure, as in naphthalene, or are attachedvia one or more carbon-carbon bonds, as in biphenyl.

At certain places, the definitions or aspects refer to specific rings(e.g., an azetidine ring, a pyridine ring, etc.). Unless otherwiseindicated, these rings can be attached to any ring member provided thatthe valency of the atom is not exceeded. For example, an azetidine ringmay be attached at any position of the ring, whereas an azetidin-3-ylring is attached at the 3-position.

As used herein, the term “electron withdrawing group” (EWG), employedalone or in combination with other terms, refers to an atom or group ofatoms substituted onto a π-system (e.g., substituted onto an aryl orheteroaryl ring) that draws electron density away from the π-systemthrough induction (e.g., withdrawing electron density about a σ-bond) orresonance (e.g., withdrawing electron density about a π-bond orπ-system). Example electron withdrawing groups include, but are notlimited to, halo groups (e.g., fluoro, chloro, bromo, iodo), nitriles(e.g., —CN), carbonyl groups (e.g., aldehydes, ketones, carboxylicacids, acid chlorides, esters, and the like), nitro croups (e.g., —NO₂),haloalkyl groups (e.g., —CH₂F, —CHF₂, —CF₃, and the like), alkenylgroups (e.g., vinyl), alkynyl groups (e.g., ethynyl), sulfonyl groups(e.g., S(O)R, S(O)₂R), sulfonate groups (e.g., —SO₃H), and sulfonamidegroups (e.g., S(O)N(R)₂, S(O)₂N(R)═). In various aspects, the electronwithdrawing group is selected from the group consisting of halo, C₂-C₆alkenyl, C₂-C₆ alkynyl, C₁-C₃ haloalkyl, ON, NO₂, C(═O)OR^(al),O(═O)R^(bl), C(═O)NR^(cl)R^(dl), C(═O)SR^(el), —NR^(cl)S(O)R^(el),—NR^(cl)S(O)₂R^(el), S(═O)R^(el), S(═O)₂R^(el), S(═O)NR^(cl)R^(dl),S(═O)₂NR^(cl)R^(dl), and P(O)(OR^(al))₂. In various aspects, theelectron withdrawing group is selected from the group consisting ofC(═O)OR^(al), C(═O)R^(bl), C(═O)NR^(cl)R^(dl), C(═O)SR^(el),S(═O)R^(el), S(═O)₂R^(el), S(═O)NR^(cl)R^(dl), and S(═O)₂NR^(cl)R^(dl).In various aspects, the electron withdrawing group is C(═O)OR^(al). Invarious aspects, the electron withdrawing group is C(═O)OR^(al), whereinR^(al), R^(bl), R^(cl), R^(dl), and R^(el) are independently selected ateach occurrence from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,heterocycloalkyl, aryl, or heteroaryl, each of which R^(al), R^(bl),R^(cl), R^(dl), or R^(el) may be optionally substituted with one or moresubstituents as described herein.

“R¹,” “R²,” “R³,” “R^(n),” etc., where n is some integer, as used hereincan, independently, possess one or more of the groups listed above. Forexample, if R¹ is a straight chain alkyl group, one of the hydrogenatoms of the alkyl group can optionally be substituted with a hydroxylgroup, an alkoxy group, an amine group, an alkyl group, a halide, andthe like. Depending upon the groups that are selected, a first group canbe incorporated within the second group or, alternatively, the firstgroup can be pendant (i.e., attached) to the second group. For example,with the phrase “an alkyl group comprising an amino group,” the aminogroup can be incorporated within the backbone of the alkyl group.Alternatively, the amino group can be attached to the backbone of thealkyl group. The nature of the group(s) that is (are) selected willdetermine if the first group is embedded or attached to the secondgroup.

Unless stated to the contrary, a formula with chemical bonds shown onlyas solid lines and not as wedges or dashed lines contemplates eachpossible isomer, e.g., each enantiomer, diastereomer, and meso compound,and a mixture of isomers, such as a racemic or scalemic mixture.

Dashed lines in a chemical structure are used to indicate that a bondmay be present or absent, or that it may be a delocalized bond betweenthe indicated atoms.

Preparation of the compounds described herein can involve a reaction inthe presence of an add or a base. Example acids can be inorganic ororganic adds and include, but are not limited to, strong and weak acids.Example adds include, but are not limited to, hydrochloric add,hydrobromic add, sulfuric acid, phosphoric acid; p-toluenesulfonic add,4-nitrobenzoic acid, methanesulfonic add, benzenesulfonic add,trifluoroacetic acid, and nitric acid. Example weak adds include; butare not limited to, acetic acid, propionic acid, butanoic acid; benzoicacid, tartaric acid, pentanoic add; hexanoic add, heptanoic add,octanoic acid, nonanoic add, and decanoic add. Examples of basesinclude, without limitation, lithium hydroxide, sodium hydroxide,potassium hydroxide, lithium carbonate, sodium carbonate, potassiumcarbonate, sodium bicarbonate; and amine bases. Example strong basesinclude, but are not limited to, hydroxide, alkoxides, metal amides,metal hydrides, metal dialkylamides, and arylamines, wherein; alkoxidesinclude lithium, sodium and potassium salts of methyl, ethyl and t-butyloxides; metal amides include sodium amide, potassium amide and lithiumamide, metal hydrides include sodium hydride, potassium hydride andlithium hydride; and metal dialkylamides include lithium, sodium, andpotassium salts of methyl, ethyl, n-propyl, iso-propyl, n-butyl,t-butyl, trimethylsilyl and cyclohexyl substituted amides (e.g., lithiumN-isopropylcyclohexylamide).

The following abbreviations may be used herein: AcOH (acetic acid); aq.(aqueous); atm. (atmosphere(s)); Br₂ (bromine); Bn (benzyl); calc.(calculated); d (doublet); dd (doublet of doublets); DCM(dichloromethane); DMF (N,N-dimethylformamide); Et (ethyl); Et₂O(diethyl ether); EtOAc (ethyl acetate); EtOH (ethanol); EWG (electronwithdrawing group); g (gram(s)); h (hour(s)); HCl (hydrochloricadd/hydrogen chloride); HPLC (high performance liquid chromatography);H₂S₄ (sulfuric add); Hz (hertz); (iodine); IPA (isopropyl alcohol); J(coupling constant); KOH (potassium hydroxide); K₃PO₄ (potassiumphosphate); LCMS (liquid chromatography-mass spectrometry); GC (gaschromatography), DCA (lithium N-isopropylcyclohexylamide); m(multiplet); M (molar); MS (Mass spectrometry); Me (methyl); MeCN(acetonitrile); MeOH (methanol); mg (milligram(s)); min, (minutes(s));mL (milliliter(s)); mmol (millimole(s)); N (normal); NaBH₄CN (sodiumcyanoborohydride); NHP (N-heterocyclic phosphine); NHP—C1(N-heterocyclic phosphine chloride); Na₂CO₃ (sodium carbonate); NaHCO₃(sodium bicarbonate); NaOH (sodium hydroxide); Na₂SO₄ (sodium sulfate);nM (nanomolar); NMR (nuclear magnetic resonance spectroscopy); PCb(trichlorophosphine); PMP (4-methoxyphenyl); RP-HPLC (reverse phase highperformance liquid chromatography); t (triplet or tertiary); t-Bu(teri-butyl); TEA (triethylamine); TFA (trifluoroacetic acid); THF(tetrahydrofuran); TLC (thin layer chromatography); μg (microgram(s));μL (microliter(s)); μM (micromolar); wt % (weight percent).

Notwithstanding that the numerical ranges and parameters setting forththe broad scope of the disclosure are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. Any numerical value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Furthermore, when numerical ranges ofvarying scope are set forth herein, it is contemplated that anycombination of these values inclusive of the recited values may be used.Further, ranges can be expressed herein as from “about” one particularvalue, and/or to “about” another particular value. When such a range isexpressed, another aspect includes from the one particular value and/orto the other particular value.

Similarly, when values are expressed as approximations, by use of theantecedent “about,” it will be understood that the particular valueforms another aspect. It will be further understood that the endpointsof each of the ranges are significant both in relation to the otherendpoint and independently of the other endpoint. Unless statedotherwise, the term “about” means within 5% (e.g., within 2% or 1%) ofthe particular value modified by the term “about.”

As used herein, the term “composition” is intended to encompass aproduct comprising the specified ingredients in the specified amounts,as well as any product which results, directly or indirectly, from acombination of the specified ingredients in the specified amounts.

References in the specification and concluding claims to parts by weightof a particular element or component in a composition denotes the weightrelationship between the element or component and any other elements orcomponents in the composition or article for which a part by weight isexpressed. Thus, in a mixture containing 2 parts by weight of componentX and 5 parts by weight component Y, X and Y are present at a weightratio of 2:5, and are present in such ratio regardless of whetheradditional components are contained in the mixture.

A weight percent (wt. %) of a component, unless specifically stated tothe contrary, is based on the total weight of the formulation orcomposition in which the component is included.

Reference will now be made in detail to specific aspects of thedisclosed materials, compounds, compositions, articles, and methods,examples of which are illustrated in the accompanying Examples andFigures.

Methods

As summarized above, disclosed herein are the methods comprisingselectively deoxygenating an aromatic compound having at least onehydroxyl group in the presence of a hydrogen gas and a catalyst systemto form a reaction product, wherein the catalyst system comprises acatalyst of formula (I):

In such aspects, R¹ is hydrogen, OH, O⁻, halogen, amine, C₁-C₁₀ alkyl,C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃heteroaryl, C₆-C₁₄ aryloxy, C₃-C₁₀ cycloalkyl, or C₃-C₁₀ cycloalkenyl,wherein R¹ is optionally substituted with C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy,C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl,aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone,nitro, cyano, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol, orphosphonyl;

-   each R² is, independent of the other, C₁-C₁₀ alkyl, C₂-C₁₀ alkenyl,    C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃ heteroaryl, wherein R² is    optionally substituted with C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀    alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde,    amino, carboxylic acid, ester, ether, halide, hydroxy, ketone,    nitro, cyano, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or    thiol; each R³ and R⁴ are, independent of the other, hydrogen,    C₁-C₁₀ alkyl, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃    heteroaryl, wherein R³ and R⁴ are optionally substituted with C₁-C₁₀    alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C2-C10 alkynyl, C₆-C₁₄ aryl,    C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic acid, ester, ether,    halide, hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo, sulfonyl,    sulfone, sulfoxide, or thiol, or R³ and R⁴ combine together with the    atoms to which they are attached to form a cycloalkyl,    cycloheteroaryl, aryl, or heteroaryl; each R¹⁶ and R¹⁷ are,    independent of the other, hydrogen, OH, O⁻, halogen, amine, C₁-C₁₀    alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl,    C₁-C₁₃ heteroaryl, C₆-C₁₄ aryloxy, C₃-C₁₀ cycloalkyl, or C₃-C₁₀    cycloalkenyl, wherein each R¹⁶ and R¹⁵, independent of the other, is    optionally substituted with C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀    alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde,    amino, carboxylic acid, ester, ether, halide, hydroxy, ketone,    nitro, cyano, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol,    phosphonyl;-   M is Ru or Ir;-   each L is independently selected from Cl, Br, CH₃CN, DMF, H₂O,    bipyridine, phenylpyridine, CO₂, and a CNC-pincer ligand; and-   n is 1, 2, or 3.

In some aspects, the aromatic compound having at least one hydroxylgroup can have a formula (II):

wherein,

-   R⁵ is independently selected from hydrogen, substituted or    unsubstituted C₁-C₆-alkyl; R¹¹—OH; —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,    substituted or unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls,    C₂-C₁₀ alkenyl, and Ar′;-   R⁶ is independently selected from hydrogen, hydrogen, substituted or    unsubstituted R¹¹—OH; —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹, substituted or    unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl,    and Ar′;-   R⁷ is independently selected from hydrogen, substituted or    unsubstituted C₁-C₆-alkyl, R¹¹—OH, —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,    substituted or unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls,    C₂-C₁₀ alkenyl, and Ar′;-   R⁸ is independently selected from hydrogen, substituted or    unsubstituted C₁-C₆-alkyl, R¹¹—OH; —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,    substituted or unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls,    C₂-C₁₀ alkenyl, and Ar′;-   R⁹ is independently selected from hydrogen, substituted or    unsubstituted C₁-C₆-alkyl, R¹¹—OH; —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,    substituted or unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls,    C₂-C₁₀ alkenyl, and Ar′;-   R¹⁰ is independently selected from hydrogen, substituted or    unsubstituted C₁-C₆-alkyl; R¹¹—OH; —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,    substituted or unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls,    C₂-C₁₀ alkenyl, and Ar′;-   wherein when R⁶, R⁷, R⁹, and R¹⁰ are all hydrogen, R⁵ is R¹¹—OH,    R¹⁸OR¹⁹, or R²⁰COR²¹;-   wherein R¹¹ is a bond, substituted or unsubstituted C₁-C₆ alkyl,    C₂-C₁₀ alkenyl, or Ar″;-   R¹² is independently selected from hydrogen, substituted or    unsubstituted C₁-C₆ alkyl, C₂-C₁₀ alkenyl, and Ar′″,-   R¹⁸ is independently selected from substituted or unsubstituted    C₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀ cycloalkyls and    heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;-   R¹⁹ is independently selected from substituted or unsubstituted    C₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀ cycloalkyls and    heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;-   R²⁰ is independently selected from a bond, substituted or    unsubstituted C₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀    cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;-   R²¹ is independently selected from hydrogen, hydroxyl, C₁-C₁₀ alkyl,    C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃    heteroaryl, C₆-C₁₄ aryloxy, C₃-C₁₀ cycloalkyl, or C₃-C₁₀    cycloalkenyl and Ar′, wherein R²¹ is optionally substituted with    C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄    aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic acid, ester,    ether, halide, hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo,    sulfonyl, sulfone, sulfoxide, thiol, phosphonyl;-   Ar′ is a C₆-C₁₄ aryl or heteroaryl group optionally substituted with    1, 2, or 3 optional substituents; and-   Ar″ is a C₆-C₁₄ aryl or heteroaryl group optionally substituted with    1, 2, or 3 optional substituents;-   Ar′″ is a C₆-C₁₄ aryl or heteroaryl group optionally substituted    with 1, 2, or 3 optional substituents; and wherein Ar′, Ar″, or    Ar′″, are the same or different.

In still further aspects, wherein R⁵ is R¹¹—OH, R¹⁸OR¹⁹, or R²⁰COR²¹, R⁶is independently selected from hydrogen, substituted or unsubstitutedC₁-C₆-alkyl, R¹¹—OH; —OR¹², substituted or unsubstituted C₃-C₁₀cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R⁷ isindependently selected from hydrogen, substituted or unsubstitutedR¹¹—OH; —OR¹², substituted or unsubstituted C₃-C₁₀ cycloalkyls andheteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R⁸ is independently selected fromhydrogen, substituted or unsubstituted R¹¹—OH; —OR¹², substituted orunsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, andAr′; wherein R⁹ is independently selected from hydrogen, substituted orunsubstituted R¹¹—OH; —OR¹², substituted or unsubstituted C₃-C₁₀cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R¹⁰ isindependently selected from hydrogen, substituted or unsubstitutedR¹¹—OH; —OR¹², substituted or unsubstituted C₃-C₁₀ cycloalkyls andheteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R¹¹ is a bond, substituted orunsubstituted C₁-C₆ alkyl, C₂-C₁₀ alkenyl, or Ar″; R¹² is independentlyselected from hydrogen, substituted or unsubstituted C₁-C₆ alkyl, C₂-C₁₀alkenyl, R¹⁸ is independently selected from substituted or unsubstitutedC₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀ cycloalkyls andheteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R¹⁹ is independently selectedfrom substituted or unsubstituted C₁-C₆-alkyl, substituted orunsubstituted 03-C10 cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, andAr′; R²⁰ is independently selected from a bond, substituted orunsubstituted C₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R²¹ isindependently selected from hydrogen, hydroxyl, C₁-C₁₀ alkyl, C₁-C₁₀alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl,C₆-C₁₄ aryloxy, C₃-C₁₀ cycloalkyl, or C₃-C₁₀ cycloalkenyl and Ar′,wherein R²¹ is optionally substituted with C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy,C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl,aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone,nitro, cyano, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol,phosphonyl; and Ar′″, Ar′ is a C₆-C₁₄ aryl or heteroaryl groupoptionally substituted with 1, 2, or 3 optional substituents; Ar″ aC₆-C₁₄ aryl or heteroaryl group optionally substituted with 1, 2, or 3optional substituents; Ar′″ a C₆-C₁₄ aryl or heteroaryl group optionallysubstituted with 1, 2, or 3 optional substituents; and wherein Ar′, Ar″,and Ar′″ are same or different.

In certain aspects, the oxygenated aromatic compound can comprisevarious oxygen containing groups. In still further aspects, theoxygenated aromatic compound can comprise more than one oxygen group. Insome aspects, the oxygenated compounds can comprise a hydroxyl group. Instill further aspects, the term “oxygenated aromatic compounds” caninclude, without limitations, any known in the art phenols, alkylphenols, alkoxy-substituted aromatic compounds (for example, and withoutlimitation, anisole and substituted anisoles), and aromatic carbonylcompounds. The oxygenated compounds also can comprise aliphaticoxygenates such as alcohols and carbonyls.

In yet other aspects, the oxygenated compound can comprise more than onehydroxyl group. In certain aspects, the aromatic compound can compriseat least two hydroxyl groups. In still further aspects, the aromaticcompound can comprise more than two hydroxyl groups.

It is understood that the aromatic compound can comprise oxygencontaining groups in any position on an aromatic ring. In certainaspects, when more than one oxygen containing groups are present, thisgroup can be positioned in para, meta, or ortho positions on thearomatic ring.

In still further aspects, the aromatic compound having at least onehydroxyl group can be selected from

wherein R¹¹ can be a bond, substituted or unsubstituted C₁-C₆ alkyl,C₂-C₁₀ alkenyl, and Ar″; and wherein R^(11′) and R¹¹ are the same ordifferent. Yet in other aspects, R¹¹ and R^(11′) are not the same. Inyet other aspects, R¹⁸ is independently selected from substituted orunsubstituted C₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R¹⁹ isindependently selected from substituted or unsubstituted C₁-C₆-alkyl,substituted or unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls, C₂-C₁₀alkenyl, and Ar′; R²⁰ is independently selected from a bond, substitutedor unsubstituted substituted or unsubstituted C₃-C₁₀ cycloalkyls andheteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R²¹ is independently selectedfrom hydrogen, hydroxyl, C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl,C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, C₆-C₁₄ aryloxy, C₃-C₁₀cycloalkyl, or C₃-C₁₀ cycloalkenyl and Ar′, wherein R²¹ is optionallysubstituted with C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylicacid, ester, ether, halide, hydroxy, ketone, nitro, cyano, silyl,sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol, phosphonyl.

It is further understood that R¹⁸—O—R¹⁹ and R²⁰COR²¹ can be located inany position on the ring and are not limited to R⁵ position. In yetother aspects, one or more of R¹⁸—O—R¹⁹ or R²⁰COR²¹ can be present. Instill further aspects, both R¹⁸—O—R¹⁹ and R²⁰COR²¹ can be present in anyposition on the ring.

In still further exemplary aspects, the aromatic compounds can compriseany known in aromatic compounds comprising at least one hydroxyl group.In certain exemplary aspects, the aromatic compounds described hereincan comprise lignin, paracoumaryl alcohol, benzyl alcohol, coniferylalcohol, cinnannyl alcohol, sinapyl alcohol, vanillyl alcohol, anisylalcohol, veratrole alcohol, methoxybenzyl alcohol, guiacol, and theirderivatives, for example, and without limitation alkylated derivativesof the cited alcohols. In still further aspects, the aromatic compoundsdescribed herein can comprise a phenylethyl-phenyl ether and it isderivatives.

In still further aspects, the disclosed herein catalyst can be anycatalyst disclosed in U.S. Patent Application Publication No.2019/0083966, which disclosure is incorporated herein by reference inits entirety.

In a still further aspect, R¹ can be hydrogen, OH, O⁻, halogen, oroptionally substituted amine, alkyl, aryl, alkoxy, or aryloxy. In yetother exemplary aspects, R¹ is OC₁-C₁₂ alkyl, e.g., OCH₃. In otherexamples, R¹ is methoxy substituted with CO²H. In some exemplaryaspects, R¹ is not H.

In some exemplary aspects, each R² can be optionally substituted alkylor aryl. Yet, in other aspects, both R² are methyl.

In some aspects, both R³ and R⁴ can combine together with the atoms towhich they are attached to form a cycloalkyl, cycloheteroaryl, aryl, orheteroaryl. In specific examples, both R³ and R⁴ can combine togetherwith the atoms to which they are attached to form an aryl or heteroaryl.In yet other aspects, R³ and R⁴ can be the same or different. In someexemplary aspects, both R³ and R⁴ can be hydrogen.

In still further aspects, each R¹⁶ and R¹⁷, independent of the other,can be hydrogen, OH, O⁻, halogen, amine, C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy,C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, C₆-C₁₄aryloxy, C₃-C₁₀ cycloalkyl, or 03-C10 cycloalkenyl, wherein each R¹⁶ andR₁₅, independent of the other, is optionally substituted with C₁-C₁₀alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl,C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic acid, ester, ether,halide, hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo, sulfonyl,sulfone, sulfoxide, thiol, phosphonyl.

In certain aspects, M can be Ru, Pt, Pd or Ir. In still further aspects,M is Ru. In yet other aspects, M is Ir. Yet, in other aspects, M can beany transition metal capable of forming a complex with the disclosedcompounds. In certain aspects, M can comprise Fe, Co, or Ni. In yetother aspects, M can be Pt. In specific examples, M can be Ni. In otherexamples, M can be Pd. In still other examples, M can be Fe. In yetfurther examples, M can be Co.

In still further aspects, the catalyst of formula (I) can exist as ionswith a 1+, 2+, or 3+ charge. In such aspects, disclosed herein arecompounds wherein the catalyst of formula (I) is associated with one ormore counteranions. In some exemplary aspects, suitable counteranionscomprise iodide (I⁻), bromide (Br⁻), trifluoroacetate (CF₃COO⁻),triflate (OTf⁻, CF₃SO₃ ⁻), tetrafluoroborate (BF₄ ⁻), andhexafluorophosphate (PF₆ ⁻).

In certain aspects, L is Cl, Br, CH₃CN, DMF, H₂O, bipyridine orphenylpyridine. In some exemplary aspects, Lis Cl or Br. In stillfurther aspects, at least one L can be Cl. In other aspects, one or moreL can be CH₃CN. In other aspects, one or more L can be dimethylformamide(DMF). In still further aspects, one or more L can be H₂O. In stillfurther aspects, one or more L can be bipyridine or phenylpyridine. Inyet further exemplary aspects, L can be a CNC-pincer ligand. The pincerprecursor used to form the ligand is shown below:

wherein R¹, R², R³, and R⁴ can be any substituent as described herein.In certain aspects, R¹ is hydrogen, OH, O—, halogen, amino, alkyl,alkenyl, alkynyl, aryl, heteroaryl, alkoxy, aryloxy, cycloalkyl, orcycloalkenyl, wherein R¹ is optionally substituted with alkyl, alkoxy,alkenyl, alkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid,ester, ether, halide, hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo,sulfonyl, sulfone, sulfoxide, thiol, or phosphonyl. In yet otheraspects, R¹ is OH, O⁻, halogen, or optionally substituted amine, alkyl,aryl, alkoxy, or aryloxy, e.g., OC₁₋₁₂ alkyl such as OCH₃. In stillfurther aspects, R1 can be methoxy substituted with CO₂H.

In certain aspects, each R² can be, independent of the other, alkyl,alkenyl, alkynyl, aryl, or heteroaryl optionally substituted with alkyl,alkoxy, alkenyl, alkynyl, aryl, heteroaryl, aldehyde, amino, carboxylicacid, ester, ether, halide, hydroxy, ketone, nitro, cyano, silyl,sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol. In specific examples,each R² can be optionally substituted alkyl or aryl. In specificexamples, both R² are methyl.

In still further aspects, each R³ and R⁴ can be, independent of theother, hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl optionallysubstituted with alkyl, alkoxy, alkenyl, alkynyl, aryl, heteroaryl,aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone,nitro, cyano, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol,or R³ and R⁴ can combine together with the atoms to which they areattached to form a cycloalkyl, cycloheteroaryl, aryl, or heteroaryl. Inexemplary aspects, both R³ and R⁴ can combine together with the atoms towhich they are attached to form a cycloalkyl, cycloheteroaryl, aryl, orheteroaryl, preferably an aryl or heteroaryl. In other exemplaryaspects, both R³ and R⁴ can be hydrogen.

In still further aspects, each R¹⁶ and R¹⁷ can be independent of theother, hydrogen, OH, O⁻, halogen, amine, C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy,C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, C₆-C₁₄aryloxy, C₃-C₁₀ cycloalkyl, or C₃-C₁₀ cycloalkenyl, wherein each R¹⁶ andR₁₅, independent of the other, is optionally substituted with C₁-C₁₀alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl,C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic acid, ester, ether,halide, hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo, sulfonyl,sulfone, sulfoxide, thiol, or phosphonyl. In some exemplary aspects, R¹⁶and R¹⁷ can be hydrogen. In yet other exemplary and non-limitingaspects, R¹⁶ can be —O— group and R¹⁷ can be hydrogen.

Without wishing to be bound by any theory, it is believed that CNCpincer ligands can modulate electron density at the metal center withand without an electron donor group (O⁻) at the para (to N) position togreatly enhance the electron donor properties for the pyridine ring (A.A. Danopoulos, et al., Chem. Eur. J., 2009, 15, 5491-5502).

In yet other aspects, L can be a CNC pincer ligand formed from thepincer precursor as described above where R² is CH₃:

In some exemplary aspects, disclosed herein are the following rutheniumcompounds:

wherein R″ is methyl or phenyl, and X is Cl, Br, or CH₃CN,wherein n=1 wherein X is Cl or Br, and n=2 wherein X is CH₃CN.

In still further aspects, exemplary ruthenium compounds can comprise:

-   -   wherein X is Cl or NCCH₃, and wherein    -   n=1 when X is Cl; and n=2 when X is NCCH₃.

It is understood that the use of the OTf counteranions is exemplaryonly, and it can be replaced by any of the counteranions disclosedherein.

It is understood that the catalyst disclosed herein can comprise othermetals. In some exemplary aspects, the catalyst can comprise nickelcompounds, for example:

In yet other exemplary and unlimiting aspects, the following iron andcobalt compounds can be utilized:

The Br and BF₄ counteranions can be substituted with any of thecounteranions disclosed herein.

In still further aspects, the catalyst is present in an amount ofgreater than 0 mol % to about 1.5 mol %, including exemplary values ofabout 0.05 mol %, about 0.1 mol %, about 4 mol %, about 0.2 mol %, about0.3 mol %, about 0.0.5 mol %, about 0.6 mol %, about 0.7 mol %, about0.8 mol %, about 0.9 mol %, about 1.0 mol %, about 1.1 mol %, about 1.2mol %, about 1.3 mol %, and about 1.4 mol %.

In some exemplary aspects, the catalysts disclosed herein are notanchored to a substrate. In yet other aspects, the catalysts are presentin a solvent. Any known in the art solvents can be utilized, forexample, and without limitation, methanol, ethanol, isopropanol,acetonitrile, diethyl ether, tetrahydrofuran, nitromethane, and thelike.

In some exemplary and unlimiting aspects, the catalysts disclosed hereincan be anchored to a surface. In some aspects, the suitable surfaces cancomprise metal and metal oxide semiconductors such as TiO₂, NiO, SnO₂,ZnO. In yet other exemplary aspects, the surfaces comprise, withoutlimitation, glass, metal-coated glass, polymer materials, metal-coatedpolymers, metal, metal alloy, quartz, paper, transparent conductingmaterial, nanowires, and nanotubes. In some exemplary aspects, thepolymer materials are polyalkylenes, polyesters, polyamides,polycarbonates, and polyalkoxyls. In specific examples, the surface canbe Mo-coated glass, Au-coated glass, Ni-coated glass, indium tinoxide-coated glass, Mo-coated polyethylene terephthalate, Au-coatedpolyethylene terephthalate, Ni-coated polyethylene terephthalate, indiumtin oxide-coated polyethylene terephthalate, non-woven indium tin oxide,or any other suitable material. In one aspect, a surface can beelectrically conductive, for example, to carry charge to or from a filmor layer of nanocrystals. In specific examples, the surface can be ametal or metal coated surface.

In still further aspects, the catalyst system of the current disclosurefurther comprises an external acid or base. It is understood that anyknown in the art acids and bases can be utilized. In yet other aspects,the catalyst system does not comprise an external acid.

For example, and without limitation, the catalyst system can compriseinorganic acids. In yet other aspects, the inorganic acids are mineralacids. In yet other aspects, the catalyst system can comprise an organicacid. In still further exemplary aspects, the catalyst system cancomprise an inorganic base or an organic base. In yet other aspects, theacids and/or base can comprise an Arrhenius acid (base), a Lewis acid(and/or Lewis base), a Brønstead-Lowry acid (and/or Brønstead-Lowry). Instill further aspects, any known in the art acids can be used. It isunderstood that the acids can be monoprotic or polyprotic. In yet otheraspects, the bases can comprise any known in the art bases.

In still further aspects, acids (bases) can comprise a strong acid(and/or strong base), a weak acid (and/or weak base). It is understoodthat the terms “strong” acids and bases are used herein as it commonlyused in general chemistry. It is understood that the term “strong” acid(and/or base), when refers to acids (bases) that are capable of formingaqueous solutions, refers to acids (bases) that are fully dissociated inwater. The term “weak” acid (and/or base), when refers to acids (bases)that are capable of forming aqueous solutions, refers to acids (bases)that partially dissociate into their ions in water. It is furtherunderstood that the degree of the acid/base strength can be determinedbased on its level of dissociation in water.

In some exemplary aspects, the strong acids comprise hydrochloric acids(HCl), perchloric acid (HClO₄), hydrobromic acid (HBr), nitric acid(HNO₃), sulfuric acid (H₂SO₄), hydroiodic acid (HI), p-toluenesulfonicacid, or methanesulfonic acid. In still further aspects, the weak acidscan comprise acetic acid, citric acid, lactic acid, phosphoric acid,carbonic acid, hydrofluoric acid, and the like.

In still further aspects, the strong bases comprise LiOH, NaOH, KOH,Ca(OH)₂, Ba(OH)₂, Sr(OH)₂, tetramethylammonium hydroxide, sodiumtert-butoxide, and the like. The weak acids can comprise NaHCO₃, Na₂CO₃,or K₂CO₃.

In still further aspects, the catalyst system of the instant disclosurecomprises an external base. In exemplary aspects, the base can beinorganic or organic, as described above. Any known in the art bases canbe present in the disclosed catalyst system, including a strong base, aweak base, or a Lewis base.

In still further aspects, the base is present in an amount from about 50mol % to 100 mol %, including exemplary values of about 55 mol %, about60 mol %, about 65 mol %, about 70 mol %, about 75 mol %, about 80 mol%, about 85 mol %, about 90 mol %, and about 95 mol %.

In still further aspects, wherein the reaction product comprises acompound A of formula (III)

wherein R¹³ is R¹¹—H. It is understood that R⁶-R¹⁰ can be any of thedisclosed above substituents. In yet other aspects, R¹³ can be R¹⁸—H orR²⁰—H. It is understood that in such aspects, R⁶-R¹⁰ can be any of thedisclosed above substituents.

In still further aspects, when the aromatic compound comprising at leastone hydroxyl group is selected from

The compound A can comprise:

It is understood that in some aspects, the reaction product can compriseadditional compounds. In some exemplary aspects, the reaction productcan further comprise a compound B of formula (IV):

wherein R¹⁴ is —OR¹⁶, wherein R₁₅ is C₁-C₁₀ alkyl group, and R⁶-R¹⁰ canbe selected from any of the disclosed above substituents. In stillfurther aspects, when the aromatic compound comprising at least onehydroxyl group is selected from:

The compound B can comprise:

In certain aspects, the compound A is selectively formed over thecompound B. In such exemplary aspects, the selectivity of the compound Ais from about 50% to 100%, including exemplary values of about 55%,about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about90%, and about 95%. It is understood that the compound A can have anyselectivity value between any two foregoing values. For example,compound A can have selectivity from about 75% to about 90%, or fromabout 85% to 100%. In still further aspects, the compound A has a yieldfrom about 50% to 100%, including exemplary values of about 55%, about60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%,and about 95%. It is understood that the compound A can have any yieldvalue between any two foregoing values. For example, compound A can haveyield from about 75% to about 90%, or from about 85% to 100%.

Catalyst

It is understood that the catalysts disclosed herein are not limited tothe use in deoxygenation reactions only. It is further understood thatthe disclosed herein catalyst can be utilized in any reaction wheretheir catalytic efficiency in the desired range.

Also, disclosed herein are catalysts of formula (I):

-   -   wherein,    -   R¹ is hydrogen, OH, O⁻, halogen, amine, C₁-C₁₀ alkyl, C₁-C₁₀        alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃        heteroaryl, C₆-C₁₄ aryloxy, C₃-C₁₀ cycloalkyl, or C₃-C₁₀        cycloalkenyl, wherein R¹ is optionally substituted with C₁-C₁₀        alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄        aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic acid,        ester, ether, halide, hydroxy, ketone, nitro, cyano, silyl,        sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol, or phosphonyl;    -   each R² is, independent of the other, C₁-C₁₀ alkyl, C₂-C₁₀        alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃ heteroaryl,        wherein R² is optionally substituted with C₁-C₁₀ alkyl, C₁-C₁₀        alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃        heteroaryl, aldehyde, amino, carboxylic acid, ester, ether,        halide, hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo,        sulfonyl, sulfone, sulfoxide, or thiol;    -   each R³ and R⁴ are, independent of the other, hydrogen, C₁-C₁₀        alkyl, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃        heteroaryl, wherein R³ and R⁴ are optionally substituted with        C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl,        C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic        acid, ester, ether, halide, hydroxy, ketone, nitro, cyano,        silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol, or R³        and R⁴ combine together with the atoms to which they are        attached to form a cycloalkyl, cycloheteroaryl, aryl, or        heteroaryl;    -   each R¹⁶ and R¹⁷ are, independent of the other, hydrogen, OH,        O⁻, halogen, amine, C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl,        C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, C₆-C₁₄ aryloxy,        C₃-C₁₀ cycloalkyl, or C₃-C₁₀ cycloalkenyl, wherein each R¹⁶ and        R₁₅, independent of the other, is optionally substituted with        C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl,        C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic        acid, ester, ether, halide, hydroxy, ketone, nitro, cyano,        silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol,        phosphonyl;    -   M is Ru or Ir;    -   each L is independently selected from Cl, Br, CH₃CN, DMF, H₂O,        bipyridine, phenylpyridine, CO₂, and a CNC-pincer ligand; and    -   n is 1, 2, or 3.

In still some exemplary aspects, the catalyst can be selected from:

-   -   wherein R″ is methyl or phenyl, and X is Cl, Br, or CH₃CN, and        wherein n=1,    -   when X is Cl or Br, and n=2, wherein X is CH₃CN.

EXAMPLES

The following examples are set forth below to illustrate the methods andresults according to the disclosed subject matter. These examples arenot intended to be inclusive of all aspects of the subject matterdisclosed herein, but rather to illustrate representative methods,compositions, and results. These examples are not intended to excludeequivalents and variations of the present invention, which are apparentto one skilled in the art.

Efforts have been made to ensure accuracy with respect to numbers (e.g.,amounts, temperature, etc.), but some errors and deviations should beaccounted for. Unless indicated otherwise, parts are parts by weight,temperature is in ° C. or is at ambient temperature, and pressure is ator near atmospheric. There are numerous variations and combinations ofreaction conditions, e.g., component concentrations, temperatures,pressures, and other reaction ranges and conditions that can be used tooptimize the product purity and yield obtained from the describedprocess. Only reasonable and routine experimentation will be required tooptimize such process conditions.

All solvents were dried on a glass contour solvent purification systembuilt by Pure Process Technology, LLC or were used through commerciallyavailable dry solvents. Other commercially available reagents were usedwithout further purification necessary. All reactions were prepared andexecuted under an inert N_(2(g)) environment utilizing Schlenk linetechniques or glovebox and oven or flame dried flask. Purifications wereconducted open to air unless otherwise stated.

NMR spectra were recorded in a Bruker AVANCE 360 (360 MHz, 1H frequency)or AVANCE 500 (500 MHz, ¹H frequency) NMR spectrometer. FT-IR spectrawere recorded in a Bruker Alpha ATR-IR spectrophotometer. Mass spectrawere obtained in a Waters AutoSpec-Ultima NT mass spectrometer or WatersXero G2-XS QTOF. Elemental analyses were done by Atlantic Microlab, Inc.Electrochemical analysis was conducted with a CH Instrumentspotentiostat (CHI-600E). UV-Vis spectra were recorded with an OceanOptics FLAME-CHEM-UV-VIS instrument and a cuvette with 1 cm path lengthin an ambient atmosphere.

¹H and {¹H}¹³C chemical shifts in NMR were assigned with respect to theresidual peaks from deuterated NMR solvents (Gottlieb, H. E.; et al.,The Journal of Organic Chemistry 1997, 62, 7512-7515). No reference wasused for 19F chemical shifts, only the number of peaks are checked.

Additional examples can be found in “Determining the Catalyst Propertiesthat Lead to High Activity and Selectivity for CatalyticHydrodeoxygenation with Ruthenium Pincer Complexes” by E. T. Papish etal., Organometallics 2020, 39, 5, 662-669, the entire content of whichis incorporated herein by reference.

Example 1

The ability of a series of molecular ruthenium catalysts (Scheme 2)(Rodrigues, R. R.; et al., ACS Appl. Energy Mater. 2019, 2, 37-46; Das,S.; et al., Inorg. Chem. 2019, 58 (12), 8012-8020; Boudreaux, C. M.; etal., Chem. Commun. 2017, 53, 11217-11220; Burks, D. B.; et al., Chem.Commun. 2018, 54, 3819-3822) to perform selective HDO on vanillylalcohol was examined. The coordination environment around the Ru centerand the electron donating ability of the catalysts were systematicallyvaried to gain an understanding of the catalyst reactivity and how itdepends upon ligand design. The results show that the electron donorstrength of the ligands plays an important role in the catalyticactivity of these catalysts, and this work thus lays the groundwork forthe rational design of future molecular HDO catalysts.

Catalysts of type 1^(R) (as shown in Scheme 2) contain a CNC pincerfeaturing an imidazole based NHC ring bonded to a pyridine derivative.The advantage of this class of catalysts is the ease of syntheticpreparation and the ability to vary the R-group on the pyridine ring.The para position on the pyridine ring (R) can be OMe or H (Boudreaux,C. M., et al., Chem. Commun. 2017, 53, 11217-11220) or it can be OH,NMe₂ or Me. For catalysts of type 2^(R), the imidazole based NHC ring isreplaced with benzimidazole, which weakens the NHC donor strength(Rodrigues, R. R.; et al., ACS Appl. Energy Mater. 2019, 2, 37-46; Das,S.; et al., Inorg. Chem. 2019, 58 (12), 8012-8020; Boudreaux, C. M.; etal., Chem. Commun. 2017, 53, 11217-11220; Gradert, C.; et al., J.Organomet. Chem. 2014, 770, 61-68), Complex 2^(H) is previouslyunreported and was characterized by ¹H NMR, ¹³C NMR, ¹⁹F NMR, MS, and IRmethods (as described below). Catalyst 3 builds upon 2^(OMe) byreplacing methyl wingtips with phenyl wingtips on the NHC rings.Catalysts 4^(A) and 4^(B) increase the coordination number of theruthenium center and were synthesized by adding 2,2′-bipyridine (bipy)to 3 using a multistep route described previously (Burks, D. B.; et al.,Chem. Commun. 2018, 54, 3819-3822). Four of these catalysts (2^(OMe), 3,4^(A), 4^(B)) were synthesized and characterized as previously shown(Boudreaux, C. M.; et al., Chem. Commun. 2017, 53, 11217-11220). Incomparing some these catalysts to each other, the donor strength of thepincer (and extent of metal to ligand backbonding from Ru to NCCH₃ by IRspectroscopy) was found to decrease in the order 1^(OMe)>2^(OMe)>3 withthe same substituents on Ru and on the pyridine of the pincer.Furthermore, the presence of π donor R groups (e.g., OH, OMe) can resultin a more electron rich pincer.

Example 2

Vanillyl alcohol (VA) was used as a surrogate for lignin-derivedmonomers, and catalytic conversion of VA was carried out as shown inScheme 3. For all catalysts and conditions studied, the catalyticreaction yielded two major products labeled as A and B in Scheme 3 andring hydrogenation products were not observed. Product A (creosol)reduces the oxygen content of VA through the desired hydrodeoxygenationreaction. Product B (methyl vanillyl ether) is the alkylation product(Williamson ether synthesis) in methanol solvent and is considered anundesired product as it does not reduce the oxygen content of VA. Infact, control experiments in which the transition metal catalyst wasomitted (Table 1, entries 16-17) illustrate that product B can beobtained as the major product readily by treating VA with methanol underhydrogen (290 psi) in the presence of a base (44% yield) or acid (>99%yield). However, no significant yield of product A is obtained without atransition metal catalyst (Table 1, entry 15). (“Cat.” Refers to thecatalyst structures shown in Scheme 3)

TABLE 1 Screening Ruthenium Pincer Catalyst for Hydrodeoxygenation ofVanillyl Alcohol^(a) % Yield of A, Yield of B, Entry Catalyst Conv.^(b)(%)^(c) (%)^(c)  1 1^(OH)   91(1) 39.1(5) 52.2(8)  2 1^(OMe) 99.9(1)30.7(4) 69.2(4)  3 1^(NMe2) 93.6(2) 24.2(4) 69.4(3)  4 1^(Me) 99.5(4)20.9(2) 78.6(4)  5 1^(H) 18.5(4) 15.0(4)  1.9(1)  6 2^(OMe) 100.0^(d)16.8(5) 83.2(5)  7 2^(H) 99.98(1)  16.3(4) 83.7(4)  8 3 99.6(1) 21.4(7)78.2(7)  9 4^(A)   14(1)   2(2)   11(2) 10 4^(B) 100.0^(d)  2.1(2)97.9(2) 11^(e) 1^(OH) 98.0(4) 95.8(7)  0.2(1) 12^(e) 1^(OMe)   92(4)  88(5)    3(2) 13^(e) 1^(NMe2)   91(4)   89(4)  1.6(3) 14^(f) 1^(NMe2)100.0^(d)   2(1)   98(1) 15 none 19.0(8)  1.8(4) 15.5(7) 16^(g) none45.9(4)  1.9(7) 43.6(6) 17^(f) none 100.0^(d) 0.16(9) 99.95(9)  ^(a)Allexperiments were done in triplicate and analyzed by GC. Estimatedstandard deviation in the last digit is reported in parentheses.Conditions: 0.0642 M vanillyl alcohol in methanol, 1 mol % of catalyst,290 psi H₂, 100° C. for 1 h. ^(b)Conversion is calculated based onstarting material consumption. ^(c)Yield is calculated from the GC.^(d)Quantitative conversion was observed in all three experiments.^(e)50 mol % Na₂CO₃ was added. ^(f)1 mol % HOTf was added. ^(g)10 mol %Na₂CO₃ was added.

Two of the catalysts tested in Table 1 contain acidic (1^(OH)) or basic(1^(NMe2)) groups, and thus the π donor properties of the ligands can bemodified by the addition of external acids or bases (Scheme 4). Entry 11(Table 1) shows that the presence of a base (50 mol % Na₂CO₃) with1^(OH) facilitated the HDO reaction and led to a 96% yield for product Ain just 1 hour. Thus, nearly quantitative conversion to A is obtained bydeprotonating 1^(OH), which enhances the π donor properties of thepincer ligand. Furthermore, 1^(NMe2) can be deactivated by protonationof the NMe₂ group with acid (entry 14) to generate a cationic pincerligand bearing a σ withdrawing NMe₂H⁺ group. The results here looksimilar to entry 17 in Table 1, illustrating that triflic acid hascompletely deactivated 1^(NMe2). Thus, both 1^(OH) and 1^(NMe2) areswitchable HDO catalysts that can be activated or deactivated by acidsand bases (Scheme 4).

The addition of base to 1^(OMe) and 1^(NMe2) was further explored.Without wishing to be bound by any theory, it was assumed that baseshould not affect the structure of 1^(OMe) and thus any changes inobserved reactivity would not be attributed to changes in the catalyst.As illustrated by entry 12 of Table 1, using a base with 1^(OMe) togenerate 88% yield of A showing that the base accelerates the HDOreaction even in the absence of a protic ligand (cf. entry 2 with 31%yield of A). Adding a base to 1^(NMe2) would ensure that the basic aminogroup is neutral (rather than partially protonated) and thus lead to abetter π donor group. Entry 13 shows that the addition of base enhancescatalysis with 1^(NMe2), and an 89% yield of the HDO product is obtained(vs. 24% without base, entry 3). A comparison of these resultsdemonstrated that the selectivity to the desired product is increasedwith the base present for all three catalysts: 1^(R) where R═OH, OMe,NMe2. This also gives insight into H2 activation reaction, which likelyoccurs via Ru+H₂→Ru—H+H⁺. Again, without wishing to be bound by anytheory, it is speculated that the generation of H⁺ can be detrimental tothe reaction selectivity likely by promoting a Williamson ethersynthesis reaction to form the undesired product B. Thus, it was assumedthat the base can play two roles: preventing acid build up and undesiredpathways, and, when the catalyst is designed properly, the base canfurther activate the catalyst. However, base alone does not lead to thedesired product A (entry 16, Table 1). To further enhance the catalyticactivity, the experimental conditions were systematically varied.Increasing reaction temperature did not have a significant effect onreaction selectivity or activity (as shown below). In addition, catalystdecomposition was observed at temperatures>150° C.

Further, the identity and loading of the base were explored (Table 2).It was shown that strong bases such as NaOH and NaOtBu can have adetrimental effect on the reaction (entries 1 and 2). Weak bases, on theother hand, such as Na₂CO₃, can result in optimal conversion andselectivity at high base loadings (entries 4-9). The use of a very weakbase (NaHCO₃, entry 3) did not lead to good conversion. It was shownthat the quantitative formation of A can be achieved at the conditionswhere 50 or 100 mol % of Na₂CO₃ and 1 mol % of 1^(OH) are used.

TABLE 2 Hydrodeoxygenation of Vanillyl Alcohol with 1^(OH). Evaluatingthe Identity and Quantity of Base^(a) % Yield of A, Yield of B, EntryBase (mol %) Conv.^(b) (%)^(c) (%)^(c) 1 NaOtBu (10) 41.6(4) 38.1(4)1.65(6) 2 NaOH (10) 50.8(8)   47(1)  2.1(1) 3 NaHCO₃ (10) 29.2(8)  27(1)  0.6(2) 4 K₂CO₃ (10) 51.1(5) 46.8(6)  0.8(6) 5 Na₂CO₃ (1.1)  20(2)   16(2)  0.5(2) 6 Na₂CO₃ (10)   51(2)   48(2)  1.1(2) 7 Na₂CO₃(25)   73(1) 69.5(4)   2(1) 8 Na₂CO₃ (50) 98.0(4) 95.8(7)  0.2(1) 9Na₂CO₃ (110) 99.73(6)  98.8(3)  0.4(3) ^(a)All experiments were done intriplicate and analyzed by GC. Estimated standard deviation in the lastdigit is reported in parentheses. Conditions: 0.0642 M vanillyl alcoholin methanol, 1 mol % of catalyst, 290 psi H₂, 100° C. for 1 h.^(b)Conversion is calculated based on starting material consumption.^(c)Yield is calculated from the GC.

As described in detail below, using product B as a substrate and underoptimal catalytic conditions (with 1^(OH) or 1^(OMe) as the catalyst), aslower formation of A can be achieved when compared to the conversion ofVA directly to A. Without wishing to be bound by any theory, it wasproposed that product B formation does not facilitate the formation ofA. Again, without wishing to be bound by any theory, two possibilitieswere suggested: 1) B must be converted to VA by any adventitious waterpresent before the HDO reaction can occur or alternatively, 2) B goesdirectly to A, but by a mechanism that is different from that employedwhen VA is a starting material, and it must be inherently slower. Themethylated substrate B is not expected to bind to ruthenium as readilyas deprotonated VA.

Once the optimum base loadings were established, a lower catalystloading of 1^(OH) was further investigated to probe whether the catalystcan operate efficiently under very dilute conditions. Without increasingthe reaction time beyond one hour, the lowest catalyst loading thatresults in quantitative conversion to product A was 0.05 mol %(Na₂CO₃=2.5 mol %, T=150° C., TON=2,000). By lowering the temperature to100° C., quantitative conversion can be obtained with 0.01 mol %catalyst loading in 3 days (Na₂CO₃=0.5 mol %, TON=10,000). Surprisingly,an increase in the turnover number of five-fold was achieved. Thisincrease can be further increased at either lower catalyst loadings orlonger reaction times. Catalyst 1^(OH) performs better thanheterogeneous catalysts in the literature which only achieve 90% yieldof product A (Hao, P.; et al., ACS Catal. 2018, 8 (12), 11165-11173) orwhich achieve similar results (>99% yield of A and selectivity) but onlyat much higher (e.g., 5 wt. % for Zn/Pd/C) catalyst loadings (DeLucia,N. A.; et al., Catal. Today 2018, 302, 146-150; DeLucia, N. A.; et al.,ACS Catal. 2019, 9060-9071).

Example 3

For every catalytic system, there is a need to interrogate whether theactive catalyst is homogeneous or heterogeneous in nature. To probe thisissue for 1^(OH), the mercury test, as shown below, was performed. Sincemercury is known to coat the surface of nanoparticles, typically a loweractivity is observed for heterogeneous systems (Anton, D. R.; et al.,Organometallics 1983, 2 (7), 855-859; Widegren, J. A.; et al., J. Am.Chem. Soc. 2003, 125 (34), 10301-10310; Eberhard, M. R., Org. Lett.2004, 6 (13), 2125-2128).

When entry 8 of Table 2 was repeated with a few drops of mercury addedto the reaction vessel, a 95% yield of A by GC was obtained (done intriplicate). Since, within experimental error, this result is the sameas entry 8, it was assumed that mercury does not alter the catalyticactivity of 1^(OH) with 50 mol % Na₂CO₃ at 100° C. Without wishing to bebound by any theory, it was suggested that this catalyst is homogeneousand molecular under these conditions. It is understood, however, thenature of the true catalyst in solution is often sensitive to thespecific conditions employed, and therefore, caution is needed indeciding the nature of the catalyst (Stracke, J. J.; et al., ACS Catal.2013, 1209-1219; Bayram, E.; et al., J. Am. Chem. Soc. 2011, 133 (46),18889-18902).

Similarly, since the catalyst 1^(OMe) with 50 mol % Na₂CO₃ present(entry 12, Table 1) showed a large run variation in results, the mercurytest on this system was performed as well. Similar results of 91(4)%conversion, 88(4)% yield of A, 2(1)% yield of B were obtained. Again,without wishing to be bound by any theory, it was suggested that thevariation seen is not due to nanoparticle formation for 1^(OMe) withbase.

In this study, the electronic properties of ruthenium pincer complexes,along with the ability to provide free sites for substrate binding, wererelated to the ability for these complexes to function as HDO catalysts.At least one labile site was found to be necessary for any catalyticactivity (e.g., for the formation of the methylation product, B) to beobserved. Two to three labile ligand sites, however, proved necessarybut not sufficient for good yields of the HDO product A. The best yieldsand selectivity for A were achieved with the most electron rich pincerligand (1 rather than 2 or 3) with π donor substituents (1^(NMe2),1^(OMe), 1^(OH)) in the presence of a weak base (Na₂CO₃). Under lowcatalyst loadings (0.01 mol %), 1^(OH) in the presence of base serves asa homogeneous catalyst that is able to achieve a quantitative andselective conversion of vanillyl alcohol to the desired HDO product, A.

Example 4 1.1 Synthesis of 2,6-bis(1H-benzo[d]imidazol-1-yl)pyridine (7)

The compound was synthesized similarly to the procedures known in theart (Herbst, A.; et al., Organometallics 2013, 32, 1807-1814) andaccording to Scheme 5, as shown below.

NaH (1.014 g, 25.32 mmol, 3.0 eq.) was added to a 3-necked round bottomflask. Under N₂, compound 5 (2.89 g, 24.48 mmol, 2.9 eq) in dry DMF (50mL) was added to the flask. After stirring for 1 hour, compound 6 (2.0g, 8.44 mmol, 1.0 eq.) was added to the reaction flask and heatedovernight at 60° C. Then, the flask was heated at 140° C. for 2 days.The reaction was cooled to room temperature and treated with H₂O. A pinkto light brown precipitate was collected as the crude product. The crudeproduct was purified by recrystallization in ^(i)PrOH, and compound 7was obtained as pink to white crystal (1.3 g, 49.5% yield). ¹H NMR (360MHz, CDCl3) δ 8.68 (s, 2H), 8.18-8.13 (m, 3H), 7.94-7.91 (m, 2H), 7.60(d, 2H, J_(HH)=8.00 Hz), 7.45-7.40 (m, 2H).

1.2 Synthesis of the Preligand3,3′-(pyridine-2,6-diyl)bis(1-methyl-1H-benzo[d]imidazol-3-ium) triflate(8)

Compound 7 (250 mg, 0.803 mmol, 1.0 eq.) was added in a 3-necked roundbottom flask with dry DMF. Under N₂, MeOTf (0.91 mL, 8.03 mmol, 10.0eq.) was added drop wisely with stirring at 0° C. The reaction wasallowed to warm up to room temperature and stirred overnight at roomtemperature. The reaction mixture was concentrated under vacuum, thenwashed with Et₂O for 7 times, followed by washing with DCM for 7 times.Ligand 8, according to Scheme 6, was obtained as a pure white powder(253.6 mg, 49.4%). ¹H NMR (360 MHz, DMSO, ppm)³ δ 10.59 (s, 2H), 8.75(t, 1H, J_(HH)=8.03 Hz), 8.44 (d, 2H, J_(HH)=8.19 Hz), 8.29 (d, 2H,J_(HH)=8.08 Hz), 8.20 (d, 2H, J_(HH)=8.22 Hz), 7.84 (t, 2H, J_(HH)=7.45Hz), 7.76 (t, 2H, J_(HH)=8.07 Hz), 4.27 (s, 6H); ¹⁹F NMR (339 MHz, DMSO,ppm) δ 77.75.

1.3 Synthesis of Catalyst 2^(H)

[CymRuCl₂]₂ (25 mg, 0.0408 mmol, 1.0 eq.), ligand 8 (49.6 mg, 0.0776mmol, 1.9 eq.), and MeCN (5 mL) were added to a 3-necked round bottomflask in glovebox. After sealing and moving the flask out of theglovebox, Et₃N (0.114 mL, 0.816 mmol, 20.0 eq.) was added to the flaskby using a syringe and needle. The flask was then purged with N₂. Thereaction mixture was heated with stirring at 60° C. for 24 hours. Aftercooling to room temperature, the liquid was separated from the solidcrude product. The solid was washed by using Et₂O for 3 times. Thecombined liquid was diluted with Et₂O to recover more product. Catalyst2^(H), according to Scheme 7, was obtained as bright yellow solid (30.8mg, 64.9%). ¹H NMR (500 MHz, DMSO, ppm) δ 8.49 (d, 2H, J_(HH)=7.83 Hz),8.36 (d, 2H, J_(HH)=8.26 Hz), 8.17 (t, 1H, J_(HH)=8.26 Hz), 7.97 (d, 2H,J_(HH)=8.04 Hz), 7.65-7.58 (m, 4H), 4.42 (s, 6H), 2.86 (s, 3H), 2.05 (s,3H); {¹H}¹³C NMR (126 MHz, DMSO, ppm) δ 207.25, 155.61, 139.90, 136.10,131.27, 128.55, 124.62, 124.38, 124.10, 111.79, 111.71, 106.69, 34.21,3.77, 3.61; ¹⁹F NMR (339 MHz, DMSO, ppm) δ 77.75. HRMS (ESI) calculatedfor C₂₁H₁₇N₅ClRu (M-triflate-2×MeCN): 476.0216, found 476.0216. FT-IR(ATR, cm⁻¹): 3564.16, 3117.62, 2985.62, 2927.87, 2274.85, 1618.54,1594.06, 1569.22, 1479.49, 1437.82, 1393.25, 1363.34, 1326.67, 1255.32,1223.16, 1187.31, 1160.60, 1146.53, 1091.85, 1028.56, 959.65, 927.18,870.73, 842.88, 809.68, 781.10, 743.53, 733.24, 678.09, 636.97, 573.87,548.26, 516.80, 459.22, 431.61.

1.4 General Procedures

To a 20 mL vial with a stir bar, 1^(OH) (2 mg, 0.00321 mmol), vanillylalcohol (49.5 mg, 0.321 mmol), and Na₂CO₃ (8.5 mg, 0.08025 mmol), wereadded. Methanol (5 mL) was injected into the vial by using a syringe andneedle right before placing the vial in the Parr vessel. The reactionvial was semi submerged into about 350 mL methanol in a Parr vessel,which contained a metal frame to support the reaction vessel and stirbar at the bottom. The Parr vessel was sealed and purged with ultra-highpurity H2 gas for 5 times. The Parr vessel was then pressurized to 290psi (20 bar) and heated at 100° C. with stirring for 1 hr. After heatingwas completed, the Parr vessel was cooled with a water-ice bath to about40° C. After releasing the pressure, a sample was taken from thereaction mixture for GC analysis.

1.5 Method for Gas Chromatography

1 μL of the sample was injected into the inlet at 250° C. with pressure27.8 psi. 1/10 of the sample was split into the column with a flow rateof 3.0 mL/min and pressure 27.8 psi. The column was kept at 80° C. for 1min, then heated to 200° C. with a heating ramp rate of 15° C./min. Thetemperature was held for 2 min after reaching 200° C.

1.4 Optimizing the Catalyst Loading at 4 h Reaction Time

As shown in Table 3, a substantially quantitative conversion can stillbe maintained at 2.5 mol %. At 1 mol %, it is not a quantitativeconversion, but it leaves room for optimization. Therefore, 1 mol % wasused for further optimization.

TABLE 3 Hydrodeoxygenation of Vanillyl Alcohol with 1^(OH) and Na₂CO₃:Optimize Catalyst Loading at 4 h Reaction Time.^(a) Amount Amount of %Yield of Yield of Entry of 1^(OH) Na₂CO₃ Conv.^(b) A, (%)^(c) B, (%)^(c)1   5 mol % No base 74.7(2) 59(3) 14(2) 2   5 mol % 50 mol %   99(1)96(2)  1(2) 3 2.5 mol % 25 mol % 99.65(4)  97.4(5)   0.8(6)  4   1 mol %10 mol %   86(3) 81(1)  3(3) ^(a)All experiments were done in triplicateand analyzed by GC. Conditions: vanillyl alcohol in methanol (0.0128 Mfor entries 1-2 and 0.0257 M for entry 3, and 0.0624M for entry 4), 290psi H₂, 100° C. for 4 h. 1:10 catalyst to base ration was kept forentries 2-4. ^(b)Conversion is calculated based on starting materialconsumption. ^(c)Yield is calculated from the GC.

1.5 Optimizing the Reaction Temperature

As shown in Table 4, the substantially quantitative conversion wasobserved for reaction temperature above 150° C. However, the unusualcolor change of the reaction solution was observed for temperature above160° C. Without wishing to be bound by any theory, it is believed thatsuch change can be caused by catalyst decomposition. To avoid thechanges in color, the temperature of 150° C. was chosen for furthertesting.

TABLE 4 Hydrodeoxygenation of Vanillyl Alcohol with 1^(OH) and Na₂CO₃:Optimize the Reaction Temperature.^(a) % Yield of A, Yield of B, EntryTemperature Conv.^(b) (%)^(c) (%)^(c) 1 100° C.   73(1)  69.5(4)   3(1)2 120° C. 99.97(1) 99.77(2) 0.20(2)  3 150° C. 100.0^(d) 100.0^(d) 0^(e)4 160° C. 100.0^(d) 100.0^(d) 0^(e) 5 180° C. 100.0^(d) 100.0^(d) 0^(e)^(a)All experiments were done in triplicate and analyzed by GC.Conditions: 0.0642 M vanillyl alcohol in methanol, 1 mol % 1^(OH), 25mol % Na₂CO₃, 290 psi H₂, for 1 h. ^(b)Conversion is calculated based onstarting material consumption. ^(c)Yield is calculated from the GC.^(d)Quantitative conversion was observed in all three experiments.^(e)No peak was observed in all three experiments.

1.6 Hydrodeoxygenation of Methyl Vanillyl Ether (Scheme 8)

Experiments were done for this deoxygenation reaction by using compoundB as starting material, the reaction conditions are shown in Table 5.Some product A generation was observed for the experiments. Based onthese observations, and without being bound by any theory, it washypothesized that a low selectivity obtained by using other catalysts isbecause catalysts other than 1^(OH) with base have either poor abilityto convert product B to product A or have poor ability to convertproduct B back to starting material for deoxygenation reaction. Inaddition, increasing base loading doesn't enhance the product Ageneration from product B, but can enhance conversion from vanillylalcohol to product A. This may suggest higher base loading facilitatesthe catalysis from vanillyl alcohol, which reduces the reaction time andallows less amount of product B generation.

TABLE 5 Experimental Conditions for Hydrodeoxygenation of MethylVanillyl Ether^(a) Entry Conditions Yield of A (%)^(b) 1 1^(OH) 1 mol %with   50(1) Na₂CO₃ 25 mol % 2 1^(OH) 1 mol % with 60.4(8) Na₂CO₃ 50 mol% 3 1^(OH) 1 mol % with 12.6(3) no base 4 1^(OMe) 1 mol % with 15.4(8)no base ^(a)All experiments were done in triplicate and analyzed by GC.Conditions: 0.0642 M methyl vanillyl ether in methanol, 1 mol % 1^(OH),25 mol % Na₂CO₃, 290 psi H₂, for 1 h. ^(b)Yield is calculated from theGC.

1.7 Tests Using Solids (Mostly Na₂CO₃) Leftover from Catalysis

As shown in Table 6 below, the use of 1^(OMe) as a catalyst resulted inhigh variability of results (see entry 1, Table 6 below, which shows arelatively high standard deviation in % conversion and product yields).Without wishing to be bound by any theory, it was speculated that thesolid Na₂CO₃ could provide a support for a heterogeneous catalyst. Totest this hypothesis, the solids leftover from a catalytic run (whichare mostly Na₂CO₃) were isolated. These solids were tested as a catalyst(entry 2, Table 6). However, a low % yield of A was achieved, suggestingthat these solids are not active in the formation of A. Some base-drivenformation of B does occur, as is observed for Na₂CO₃ generally.

General Procedure:

To a 20 mL vial with a stir bar, 1^(OMe) (2 mg, 0.00321 mmol), vanillylalcohol (49.5 mg, 0.321 mmol), and Na₂CO₃ (8.5 mg, 0.08025 mmol) wereadded. Methanol (5 mL) was injected into the vial by using a syringe andneedle right before placing the vial in the Parr vessel. The reactionvial was semi-submerged into about 350 mL methanol in a Parr vessel,which contains a metal frame to support the reaction vessel and stir barat the bottom. The Parr vessel was sealed and purged with ultra-highpurity H₂ gas for 5 times. The Parr vessel was then pressurized to 290psi (20 bar) and heated at 100° C. with stirring for 1 hr. After heatingwas completed, the Parr vessel was cooled with a water-ice bath to about40° C. After releasing the pressure, a sample was taken from thereaction mixture for GC analysis. The reaction mixture was then filteredthrough Celite contained in a filter pipet. The solid with Celite waswashed with 1 mL MeOH twice and dried by air briefly, and wastransferred to a new 20 mL vial with a stir bar. Vanillyl alcohol (49.5mg, 0.321 mmol) was added to the vial. Methanol (5 mL) was injected intothe vial by using a syringe and needle right before placing the vial inthe Parr vessel. The reaction vial was semi-submerged into about 350 mLmethanol in a Parr vessel, which contains a metal frame to support thereaction vessel and stir bar at the bottom. The Parr vessel was sealedand purged with ultra-high purity H2 gas 5 times. The Parr vessel wasthen pressurized to 290 psi (20 bar) and heated at 100° C. with stirringfor 1 hr. After heating was completed, the Parr vessel was cooled with awater-ice bath to about 40° C. After releasing the pressure, a samplewas taken from the reaction mixture for GC analysis.

TABLE 6 Tests Using Solids Leftover from Catalysis.^(a) % Yield of A,Yield of B, Entry Catalyst Conv.^(d) (%)^(e) (%)^(e) 1^(b) 1^(OMe)  92(4) 88(5)    3(2) 2^(c) Solid from entry 1 47.69(3)  4(2) 43.2 (2)^(a)All experiments were done in triplicate and analyzed by GC.Conditions: 0.0642 M vanillyl alcohol in methanol, 290 psi H₂, for 1 h.^(b)1 mol % 1^(OMe), 50 mol % Na₂CO₃. ^(c)Solid material (mostly(Na₂CO₃) was isolated from a reaction in entry 1 by filtering thruCelite. ^(d)Conversion is calculated based on starting materialconsumption. ^(e)Yield is calculated from the GC.

1.8 Mercury Test to Probe Homogeneous vs. Heterogeneous Catalysis

General Procedure: To a 20 mL vial with a stir bar, 1⁰H (2 mg, 0.00321mmol), vanillyl alcohol (49.5 mg, 0.321 mmol), and Na₂CO₃ (8.5 mg,0.08025 mmol) were added. A few drops of Hg were added to the vial byusing a pipet. Methanol (5 mL) was injected into the vial by using asyringe and needle right before placing the vial in the Parr vessel. Thereaction vial was semi-submerged into about 350 mL methanol in a Parrvessel, which contains a metal frame to support the reaction vessel andstir bar at the bottom. The Parr vessel was sealed and purged withultra-high purity H₂ gas for 5 times. The Parr vessel was thenpressurized to 290 psi (20 bar) and heated at 100° C. with stirring for1 hr. After heating was completed, the Parr vessel was cooled with awater-ice bath to about 40° C. After releasing the pressure, a samplewas taken from the reaction mixture for GC analysis. The results areshown in Table 7.

TABLE 7 Hg Tests for the Catalysis.^(a) % Yield of A, Yield of B, EntryCatalyst Conv.^(b) (%)^(c) (%)^(c) 1 1^(OH)  91.7(8) 40.3(7) 50.9(1)2^(d) 1^(OH)  98.3(6)   95(1)  2.9(4) 3 1^(OMe) 99.94(1)   24(2)   76(2)4^(d) 1^(OMe)   91(4)   88(4)   2(1) ^(a)All experiments were done intriplicate and analyzed by GC. Conditions: 0.0642 M vanillyl alcohol inmethanol, 1 mol % of the catalyst listed above, a few drops of Hg, 290psi H₂, for 1 h. ^(b)Conversion is calculated based on starting materialconsumption. ^(c)Yield is calculated from the GC. ^(d)50 mol % Na₂CO₃were added.

Example 5

General Considerations:

All the syntheses are done as described here. Reactions are prepared andperformed under an inert atmosphere (N₂) using glovebox or Schlenk linetechniques using oven dried glassware unless otherwise stated. Work upand purifications are done open to the air.2,6-difluoro-N,N-dimethylpyridin-4-amine was synthesized following aliterature procedure (Schlosser, M.; Bobbio, C.; Rausis, T., The Journalof Organic Chemistry 2005, 70 (7), 2494-2502). 2,6-difluoro-pyridin-3-olwas isolated as minor product while synthesizing2,6-difluoro-pyridin-4-ol form 2,6-difluoropyridine (Scheme 13).

Solvents and Reagents:

Dry solvents (either commercial or dried on a glass contour solventpurification system built by Pure Process Technology, LLC) are used forreactions unless described otherwise. Reagent grade solvents are usedfor workup and purification. All the reagents are used as received fromthe commercial supplier without further purification.

Instruments and Services:

NMR spectra are recorded in a Bruker AVANCE 360 (360 MHz, ¹H frequency)or AVANCE 500 (500 MHz, ¹H frequency) NMR spectrometer. FT-IR spectraare recorded in a Bruker Alpha ATR-IR spectrophotometer. Mass spectraare obtained in a Waters AutoSpec-Ultima NT mass spectrometer or WatersXero G2-XS QTOF. Elemental analyses are done by Atlantic Microlab, Inc.

NMR Chemical Shift Reference:

¹H and {¹H}¹³C chemical shifts are assigned with respect to the residualpeaks from deuterated NMR solvents (Gottlieb, H. E.; Kotlyar, V.;Nudelman, A., The Journal of Organic Chemistry 1997, 62 (21),7512-7515). No reference is used for ¹⁹F chemical shifts, only thenumber of peaks are checked.

SC-XRD Structure Determination:

Complexes 9, 10, 13 (same as 1^(OH)) and 13e: Single crystals ofappropriate dimension were mounted on a Mitgen cryoloop in a randomorientation. Preliminary examination and data collection were performedon a Bruker Apexll CCD-based X-ray diffractometer equipped with anOxford N-Helix Cryosystem low temperature device and a fine focusMo-target X-ray tube (λ=0.71073 Å) operated at 1500 W power (50 kV, 30mA). The X-ray intensities were measured at low temperature (223 (2) K).The collected frames were integrated with the Saint (Bruker Saint Plus,Saint Plus 8.34 A; Bruker AXS Inc.: Madison, Wisconsin, USA, 2007)software using a narrow-frame algorithm. Data were corrected forabsorption effects using the multi-scan method in SADABS (Bruker SADABS,TWINABS, SADABS 2012/1; Bruker AXS Inc.: Madison, Wisconsin, USA, 2001).The space groups were assigned using XPREP of the Bruker SheIXTL(Sheldrick, G. M., Acta Crystallographica Section A 2008, 64 (1),112-122) package, solved with SheIXT (Sheldrick, G. M., ActaCrystallographica Section A 2008, 64 (1), 112-122 and refined withSheIXL (Sheldrick, G. M., Acta Crystallographica Section A 2008, 64 (1),112-122) and the graphical interface ShelXle (Hübschle, C. B.;Sheldrick, G. M.; Dittrich, B., J. Appl. Cryst. 2011, 44, 1281-1284.)and Olex2 (Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J.A. K.; Puschmann, H., J. Appl. Crystallogr. 2009, 42 (2), 339-341). Allnon-hydrogen atoms were refined anisotropically. H atoms attached tocarbon were positioned geometrically and constrained to ride on theirparent atoms. Specific structure determination details are listed inTables 8-11. Molecular diagrams of complexes 9, 10, 11 (same as1^(NMe2)), 12, 13e, and 13 (same as 1^(OH)) based on crystallographicdata with hydrogen atoms (except for H-bonded one in 13) andcounter-anions removed for clarity shown in FIG. 1 . The adherence toBeer's law and normalized absorption spectra in acetonitrile forcompounds 9, 10, 11 (same as 1^(NMe2)), 12, and 13 (same as 1^(OH)) isshown in FIG. 2 .

TABLE 8 Comparison of selected bond lengths ((in Å) in Ru-CNC pincercomplexes - 9, 10, 11 (1^(NMe2)), 12, 13e, and 13. Ru-C_(avg.) Ru-N_(py)Ru-Cl Complex 9 2.062(2) 1.997(2) 2.4108(6)  Complex 10 2.061(7)1.991(3) 2.426(1) Complex 11 2.069(4) 1.999(3) 2.407(1) Complex 122.057(4) 1.998(2) 2.4321(6)  Complex 13e 2.051(4) 1.999(3) 2.430(2)^(a)Complex 13 2.048(5) 1.999(9) 2.428(4) ^(a)average of pyridinol andpyridinone units.

TABLE 9 Selected metric parameters for the crystal structures ofcomplexes 9 and 10. Complex 9 Complex 10 Crystal data Chemical formulaC₁₈H₂₁ClN₇RU• C₁₈H₂₁N₇OClRU• CF₃SO₃ CF₃SO₃ M_(r) 621.01 637.01 CrystalSystem, Monoclinic, P2₁/c Monoclinic, P2₁/c Space group Temperature (K)223 K 223 a = 13.7319 (5) Å a = 12.8858 (12) Å Unit cell b = 23.7671 (8)Å b = 25.125 (2) Å dimensions β = 95.596 (2)° β = 107.037 (4)° c =7.9901 (3) Å c = 8.2567 (8) Å V(Å³) 2595.28 (16) 2555.8 (4) Z 4 4Radiation type Mo K_(α) radiation, Mo K_(α) radiation, λ = 0.71073 Å λ =0.71073 Å μ(mm⁻¹) 0.84 0.86 Crystal size 0.23 × 0.20 × 0.03 0.13 × 0.09× 0.03 (mm × mm × mm) Data collection Diffractometer Bruker AXS BrukerAXS SMART APEX2 SMART APEX2 CCD diffractometer CCD diffractometerAbsorption Multi-scan Multi-scan correction SADABS V2012/1 SADABSV2012/1 (Bruker AXS Inc) (Bruker AXS Inc) No. of measured, 74994 46079independent and 7026 6321 observed [with / > 5916 5382 2σ(/)]reflections R_(int) 0.041 0.049 θ_(max), θ_(min) 29.4°, 1.7° 28.3°, 2.3°Refinement R [F² > 2σ(F²) 0.032 0.059 wR(F²) 0.084 0.124 S 1.03 1.19 No.of reflections 7026 6321 No. of parameters 321 403 No. of restraints 0117 H-atom treatment Constrained Constrained Δρ_(max), Δρ_(min) 0.69,−0.59 1.01, −0.71 (e Å⁻³)

TABLE 10 Selected metric parameters for the crystal structures ofcomplexes 11 (same as 1^(NMe2)) and 12. Complex 11 (same as 1^(NMe2))Complex 12 Crystal data Chemical formula (C₁₉H₂₄N₈ClRu)• C₂₉H₂₈N₈ClRu•(CF₃SO₃) CF₃O₃ M_(r) 650.05 774.18 Crystal System, Orthorhombic, PbcnMonoclinic, P2₁/n Space group Temperature (K) 223 K 101 (2) a = 16.922(3) Å a = 8.40020 (14) Å Unit cell b = 12.696 (2) Å b = 30.6074 (6) Ådimensions β = 96.9584 (17)° c = 24.854 (4) Å c = 12.1466 (2) Å V(Å³)5339.7 (15) 3099.99 (10) Z 8 4 Radiation type Mo K_(α) radiation, MoK_(α) radiation, λ = 0.71073 Å λ = 0.71073 Å μ(mm⁻¹) 0.83 0.725 Crystalsize 0.10 × 0.07 × 0.07 0.18 × 0.071 × 0.052 (mm × mm × mm) Datacollection Diffractometer Bruker AXS XtaLAB, Synergy SMART APEX2 R, DWSystem, CCD diffractometer HyPix diffractometer Absorption Multi-scanNumerical & correction Empirical SADABS V2012/1 CrysAlisPro (Bruker AXSInc) 1.171.40.53 No. of measured, 184351 46197 independent and 8196 9052observed [with / > 5501 7649 2σ(/)] reflections R_(int) 0.070 0.0477θ_(max), θ_(min) 30.6°, 1.6° 30.034°, 2.150° Refinement R [F² > 2σ(F²)0.056 0.0423 wR(F²) 0.190 0.0931 S 1.08 1.056 No. of reflections 81969052 No. of parameters 340 428 No. of restraints 0 0 H-atom treatmentConstrained Constrained Δρ_(max), Δρ_(min) 2.32, −1.33 1.38, −1.07 (eÅ⁻³)

TABLE 11 Selected metric parameters for the crystal structures ofcomplexes 13 (same as 1^(OH)) and 13e. Complex 13e Complex 13 (same as1^(OH)) Crystal data Chemical C₂₄H₂₅ClN₇ORu• C₁₇H₁₈ClN₇ORu.C₁₇H₁₉ClN₇O•formula CF₃SO₃ CF₃SO₃•2(C₂H₃N)•C₂N M_(r) 713.10 1216.02 Crystal System,Triclinic, P 1 Triclinic, P 1 Space group Temperature (K) 223 K 223 K a= 8.339 (5) Å a = 13.474 (4) Å α = 96.546 (7)° α = 119.411 (4)° Unitcell b = 13.091 (7) Å b = 15.275 (4) Å dimensions β = 102.773 (7)° β =110.445 (4)° c = 14.232 (8) Å c = 15.370 (4) Å γ = 101.947 (7)° γ =93.344(4)° V(Å³) 1461.4 (14) 2477.6 (12) Z 2 2 Radiation type Mo K_(α)radiation, Mo K_(α) radiation, λ = 0.71073 Å λ = 0.71073 Å u(mm-1) 0.760.83 Crystal size 0.06 × 0.05 × 0.02 0.06 × 0.04 × 0.02 (mm × mm × mm)Data collection Diffractometer Bruker AXS SMART Bruker AXS SMART APEX2APEX2 CCD diffractometer CCD diffractometer Absorption Multi-scanMulti-scan correction SADABS V2012/1 SADABS V2012/1 (Bruker AXS Inc)(Bruker AXS Inc) No. of 39958 64866 measured, independent 6521 10348 andobserved [with 5304 5898 / > 2σ(/)] reflections R_(int) 0.065 0.139θ_(max), θ_(min) 27.3°, 1.5° 26.6°, 1.6° Refinement R [F² > 2σ(F²) 0.0380.079 wR(F²) 0.087 0.250 S 1.05 1.04 No. of 6521 10348 reflections No.of 383 584 parameters No. of restraints 0 1 H-atom Constrained Mixtureof Independent and treatment Constrained Δρ_(max), Δρ_(min) 0.59, −0.751.85, −1.58 (e Å⁻³)

Complex 10 was found to have two components disorder at the CF₃SO₃ ⁻counter-anion. Restraints were applied onto one of the disorderedcomponents to make sure all atoms have similar U_(ij) components (SIMU).SADI was also applied to make sure within the triflate moiety, all bondsare sensible and similar bonds have similar distances. SAME was used tomake sure respective disordered moieties have similar geometries. Allthe atoms were subjected to rigid bond restraint (RIGU).

Complex 12: A suitable crystal was selected and mounted on a Mitegencryoloop in a random orientation on an XtaLAB Synergy R, DW system,HyPix diffractometer. The crystal was kept at 101(2) K during datacollection. Using Olex2 (Dolomanov, 0. V.; Bourhis, L. J.; Gildea, R.J.; Howard, J. A. K.; Puschmann, H., J. Appl. Crystallogr. 2009, 42 (2),339-341), the structure was solved with the SheIXT (Sheldrick, G., ActaCrystallographica Section C 2015, 71 (1), 3-8.) structure solutionprogram using Intrinsic Phasing and refined with SheIXL (Sheldrick, G.,Acta Crystallographica Section C 2015, 71 (1), 3-8_refinement packageusing Least Squares minimization using either Olex2 (Dolomanov, O. V.;Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H., J. Appl.Crystallogr. 2009, 42 (2), 339-341) or ShelXle (Hübschle, C. B.;Sheldrick, G. M.; Dittrich, B., J. Appl. Cryst. 2011, 44, 1281-1284) orboth.

Synthesis of Complex 9

2,6-di(1H-imidazol-1-yl)-4-methylpyridine (9a)

A Schlenk flask was loaded with 2,6-dichloro-4-methylpyridine (1.0 g,6.172 mmol, 1.0 equiv.), 1H-imidazole (0.924 g, 13.578 mmol, 2.2equiv.), K₂CO₃ (3.412 g, 24.688 mmol, 4.0 equiv.) and a stir-bar. Theflask was filled with DMF (20 mL) from SPS. Then the flask was connectedto a Schlenk line under N2 and sealed with a rubber septum. The reactionmixture was stirred while heating at 100° C. for two days. After coolingto room temperature, the reaction mixture was diluted with ice-cooledwater (20 mL) and extracted with ethyl acetate (3×50 mL). Combined ethylacetate part was washed with brine, dried over anhydrous MgSO₄, filteredand concentrated to get the crude product. Crude was purified by column(silica gel) chromatography using 0-10% methanol in dichloromethane aseluent to obtain the product (9a) as white solid (0.834 g, 3.703 mmol)with 60% yield. ¹H-NMR (CDCl₃, 500 MHz, ppm): δ 8.31 (apparentlysinglet, 2H); 7.60 (apparently singlet, 2H); 7.16 (apparently singlet,2H); 7.06 (s, 2H); 2.48 (s, 3H). {¹H}¹³C-NMR (CDCl₃, 126 MHz, ppm): δ154.42, 148.55, 135.23, 131.16, 116.36, 110.69, 21.84.

1,1′-(4-methylpyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium)triflate(9b)

A Schlenk flask was loaded with2,6-di(1H-imidazol-1-yl)-4-methylpyridine (0.8 g, 3.552 mmol, 1.0 equiv)and a stir-bar. The flask was filled with DMF (25 mL) from SPS. Then theflask was connected to a Schlenk line under N2 and sealed with a rubberseptum. Methyl trifluoromethanesulfonate (1.61 mL, 14.208 mmol, 4.0equiv) was added to the reaction mixture using a syringe through theseptum. Then the reaction mixture was stirred at room temperature for 16hours. After 16 hours, the reaction mixture was concentrated to about 10mL and diluted with dichloromethane (25 mL) and diethyl ether (25 mL),which resulted in a suspension. The resulting suspension was stirred for10 minutes then filtered over a fritted-funnel to obtain the product(9b) as white solid (1.67 g, 3.019 mmol) with an 85% yield. ¹H-NMR(DMSO-d6, 360 MHz, ppm): δ 10.21 (s, 2H); 8.68 (apparently singlet, 2H);8.10 (s, 2H); 8.05 (apparently singlet, 2H); 4.01 (s, 6H); 2.61 (s, 3H).{¹H}¹³C-NMR (DMSO-d6, 126 MHz, ppm): δ 156.82; 145.18; 136.12; 125.01;120.65 (q, J_(CF)=323 Hz); 119.03; 114.58; 36.56; 21.21. ¹⁹F-NMR(DMSO-d6, 339 MHz, ppm): δ −77.80.

Ru-[{Im(Me)-py(4-Me)-Im(Me)}(CH₃CN)₂Cl]triflate (9)

A Schlenk flask was loaded with [Ru(p-Cym)Cl₂]₂ (0.100 g, 0.163 mmol,1.0 equiv.),1,1′-(4-methylpyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium)triflate(0.176 g, 0.310 mmol, 1.90 equiv), triethylamine (0.23 mL, 1.630 mmol,10.0 equiv.) and a stir-bar. The flask was filled with acetonitrile (10mL), sealed with a rubber septum and connected to a Schlenk line underN₂. Then the reaction mixture was stirred while heating at 50° C. forone two days. After cooling to room temperature, reaction mixture wasfiltered. Filtrate was concentrated to obtain brownish yellow solidwhich was washed with acetonitrile (1 mL) and diethyl ether (5 mL) fivetimes to obtain the product (9) as yellow solid (0.077 g, 0.124 mmol)with 40% yield. Single crystal was grown by slow vapor diffusion ofdiethyl ether into acetonitrile solution of the compound. ¹H-NMR(DMSO-d6, 360 MHz, ppm): δ 8.38 (d, 2H, J_(HH)=1.5 Hz); 7.76 (s, 2H);7.65 (d, 2H, J_(HH)=1.5 Hz); 4.10 (s, 6H); 2.73 (s, 3H); 2.63 (s, 3H);2.10 (s, 3H). ¹⁹F-NMR (DMSO-d6, 339 MHz, ppm): δ −77.76. HRMS (ESI)calculated for RuC₁₈H₂₁N₇Cl (M-triflate): 472.0590, found 472.0595.Anal. calculated for RuC₂₁H₂₄N₆O₃F₃SCl (M+CH₃CN): C—38.10, H-3.65,N—16.93; found C—37.90, H—3.45, N—16.31. FT-IR (ATR, cm⁻¹): 3160.70,3118.12, 2983.11, 2928.06, 2268.08, 1627.71, 1578.88, 1551.48, 1479.69,1432.91, 1404.92, 1384.43, 1349.10, 1262.48, 1223.44, 1199.78, 1155.61,1098.54, 1048.07, 1028.71, 990.17, 957.68, 945.93, 877.36, 855.22,788.13, 749.45, 739.16, 698.52, 636.57, 590.26, 572.05, 563.48, 517.02,430.77.

Synthesis of Complex 10

2,6-difluoro-3-methoxypyridine (10a)

A Schlenk flask was loaded with 2,6-difluoropyridin-3-ol (0.4 g, 3.052mmol, 1.0 equiv.), K₂CO₃ (0.844 g, 6.104 mmol, 2.0 equiv.), acetone (10mL) and a stir-bar. The flask was sealed with a rubber septum andconnected to a Schlenk line under N₂. Iodomethane (0.38 mL, 6.104 mmol,2.0 equiv.) was added using a syringe through the septum. Then thereaction mixture was heated at 55° C. while stirring for five hours.After cooling to room temperature, the mixture was filtered through acelite plug. Filtrate was evaporated to dryness, and the crude productwas layered between water (10 mL) and ethyl acetate (20 mL) andseparated. Aqueous part was further extracted with ethyl acetate (2×20mL), combined ethyl acetate part was washed with brine, dried overanhydrous MgSO₄, filtered and concentrated to obtain the product (10a)as a colorless liquid (0.4 g, 2.747 mmol) with 90% yield. ¹H-NMR (500MHz, CDCl₃, ppm): δ 7.42 (m, 1H), 6.74 (m, 1H), 3.87 (s, 3H). ¹⁹F-NMR(CDCl₃, 339 MHz, ppm): δ −79.89; −84.03.

2,6-di(1H-imidazol-1-yl)-3-methoxypyridine (10c)

A Schlenk flask was loaded with 2,6-difluoro-3-methoxylpyridine (0.4 g,2.757 mmol, 1.0 equiv.), 1H-imidazole (0.413 g, 6.065 mmol, 2.2 equiv),K2003 (1.524 g, 11.028 mmol, 4.0 equiv) and a stir-bar. The flask wasfilled with DMF (10 mL) from SPS. Then the flask was connected to aSchlenk line under N2 and sealed with a rubber septum. The reactionmixture was stirred while heating at 100° C. for two days. After coolingto room temperature, the reaction mixture was diluted with ice-cooledwater (15 mL) and extracted with ethyl acetate (3×30 mL). Combined ethylacetate part was washed with brine, dried over anhydrous MgSO₄, filteredand concentrated to get the crude product. Mixture of crude products wasseparated by column (silica gel) chromatography using 0-10% methanol indichloromethane as eluent.

2-fluoro-6-(1H-imidazol-1-yl)-3-methoxypyridine or6-fluoro-2-(1H-imidazol-1-yl)-3-methoxypyridine (10b) was isolated aswhite solid (major product) along with2,6-di(1H-imidazol-1-yl)-3-methoxypyridine (10c). ¹H-NMR of 2b (CDCl₃,360 MHz, ppm): δ 8.48 (s, 1H), 7.82 (s, 1H), 7.51 (dd, 1H,J_(HH,HF)=8.6, 6.1 Hz), 7.15 (s, 1H), 6.85 (dd, 1H, J_(HH,HF)=8.6, 3.6Hz); 3.97 (s, 3H). ¹⁹F-NMR (CDCl₃, 339 MHz, ppm): δ −77.97.

10b was further reacted with 1H-imidazole (2.0 equiv.) and K₂CO₃ (4.0equiv.) at 100° C. for two more days. Finally,2,6-di(1H-imidazol-1-yl)-3-methoxypyridine (10c) was obtained as whitesolid (0.346 g, 1.434 mmol) with 52% overall yield. ¹H-NMR of 10c(CDCl₃, 360 MHz, ppm): δ 8.53 (s, 1H), 8.26 (s, 1H), 7.88 (m, 1H), 7.59(m, 1H), 7.55 (d, 1H, J_(HH)=8.6 Hz); 7.28 (d, 1H, J_(HH)=8.6 Hz); 7.22(m, 1H), 7.19 (m, 1H), 4.03 (s, 3H).

1,1′-(3-methoxypyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium)triflate(10d)

Synthesis is similar as that of 9b.1,1′-(3-methoxypyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium)triflate(10d) was obtained as white solid (0.626 g, 1.099 mmol) with 78% yield.¹H-NMR (DMSO-d₆, 360 MHz, ppm): δ 10.12 (s, 1H), 10.03 (s, 1H), 8.66 (m,1H), 8.64 (m, 1H), 8.32 (d, 1H, J_(HH)=9.4 Hz); 8.20 (d, 1H, J_(HH)=9.4Hz); 8.05 (m, 1H), 8.01 (m, 1H), 4.13 (s, 3H); 4.03 (s, 3H); 3.99 (s,3H). ¹⁹F-NMR (DMSO-d6, 339 MHz, ppm): δ −77.76.

Ru-[{Im(Me)-py(3-OMe)-Im(Me)}(CH₃CN)₂Cl]triflate (10)

Synthesis is similar as that of 9.Ru-[{Im(Me)-py(3-OMe)-Im(Me)}(CH₃CN)₂Cl]triflate (10) was obtained asyellow solid (0.069 g, 0.108 mmol) with 35% yield. ¹H-NMR (DMSO-d6, 360MHz, ppm): δ 8.38 (m, 2H); 7.83 (d, 1H, J_(HH)=9.4 Hz); 7.79 (d, 1H,J_(HH)=9.4 Hz); 7.61 (m, 2H); 4.11 (s, 3H); 4.09 (s, 3H); 4.08 (s, 3H);2.74 (s, 3H); 2.11 (s, 3H). ¹⁹F-NMR (DMSO-d6, 339 MHz, ppm): δ− 77.76.HRMS (ESI) calculated for RuC₁₈H21N₇OCl (M-triflate): 488.0539, found488.0541. Anal. calculated for RuC₁₉H₂₃N₇O₅F₃SCl (M+H₂O): C—34.84,H—3.54, N—14.97; found C—34.80, H—3.52, N—14.84. FT-IR (ATR, cm⁻¹):3515.89, 3091.49, 2931.62, 2773.66, 2084.79, 1621.33, 1584.59, 1561.09,1497.01, 1469.49, 1401.52, 1350.81, 1255.62, 1239.30, 1222.72, 1147.42,1096.00, 1028.01, 941.03, 831.91, 737.59, 697.74, 636.33, 572.13,516.45, 442.65, 426.05, 413.14.

Synthesis of Complex 11 (1^(NMe2))

2,6-difluoro-N,N-dimethylpyridin-4-amine (11a)

Inside the glovebox, a Schlenk flask was loaded with 95% NaH (0.168 g,6.640 mmol, 2.1 equiv.), DMF (15 mL) and a stir-bar and the resultingsuspension were stirred for ten minutes. 1H-imidazole (0.452 g, 6.640mmol, 2.1 equiv) was added to the above suspension portion-wise, and theresulting mixture was stirred for five minutes.2,6-difluoro-N,N-dimethylpyridin-4-amine (0.5 g, 3.162 mmol, 1.0 equiv.)was added to the reaction mixture, the flask was sealed with a rubberseptum, taken out of the box, connected to a Schlenk line under N₂, andthe reaction mixture was stirred at 70° C. for 23 hours. After coolingto room temperature, the reaction mixture was diluted with ice-cooledwater (20 mL) and extracted with ethyl acetate (3×50 mL). Combinedorganic part was washed with brine, dried over anhydrous MgSO₄,filtered, and the filtrate was concentrated to get the crude product.Recrystallization of the crude product from methanol gave the product(11a) as white solid (0.724 g, 2.846 mmol) with a 90% yield. ¹H-NMR (500MHz, CDCl₃, ppm): δ 8.32 (m, 2H); 7.61 (m, 2H); 7.19 (m, 2H); 6.40 (s,2H); 3.16 (s, 6H).

1,1′-(4-(dimethylamino)pyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium)triflate(11b)

Synthesis is similar as that of 9b.1,1′-(4-(dimethylamino)pyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium)triflate(11 b) was obtained as white solid (0.676 g, 1.160 mmol) with 59% yield.¹H-NMR (DMSO-d6, 360 MHz, ppm): δ 10.15 (s, 2H); 8.71 (s, 2H); 8.01 (s,2H); 7.25 (s, 2H); 3.99 (s, 6H); 3.21 (s, 6H).

Ru-[{Im(Me)-py(4-NMe₂)-Im(Me)}(CH₃CN)₂Cl]triflate (11) (same as1^(NMe2))

A Schlenk flask was loaded with [Ru(p-Cym)Cl₂]₂ (0.141 g, 0.230 mmol,1.0 equiv.),1,1′-(4-(dimethylamino)pyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium)triflate(0.308 g, 0.529 mmol, 2.3 equiv.), Cs₂CO₃ (0.517 g, 1.587 mmol, 6.9equiv.) and a stir-bar. The flask was filled with acetonitrile (10 mL)from SPS, connected to a Schlenk line under N₂ and sealed with a rubberseptum. Then the reaction mixture was stirred while heating at 70° C.for four hours, followed by stirring at room temperature for 16 hours.Reaction mixture was filtered through an alumina plug and the aluminaplug was washed with acetonitrile until the filtrate ran colorless.Filtrate was concentrated to obtain brownish yellow solid which waswashed with acetonitrile (2 mL) and diethyl ether (5 mL) three times toobtain the product (11 (same as 1^(NMe2))) (0.056 g, 0.086 mmol) asyellow solid with 19% yield. Single crystal was grown by slow vapordiffusion of diethyl ether into acetonitrile solution of the compound.¹H-NMR (CD₃CN, 500 MHz, rt): δ 7.95 (d, 2H, J_(HH)=2.0 Hz); 7.28 (d, 2H,J_(HH)=2.0 Hz); 6.74 (s, 2H); 4.12 (s, 6H); 3.19 (s, 6H); 2.54 (s, 3H);1.90 (s, 3H). HRMS (ESI) calculated for RuC₁₉H₂₄N₈Cl (M-triflate):501.0856, found 501.0858. Anal. calculated for RuC₂₀H₂₄N₈O₃F₃SCl (M):C—36.95, H—3.72, N—17.24; found C—37.14, H—3.53, N—17.26. FT-IR (ATR,cm⁻¹): 3456.50, 3156.55, 3090.05, 2928.97, 2821.16, 2259.70, 1631.82,1570.07, 1537.20, 1502.62, 1488.09, 1464.05, 1429.71, 1401.19, 1348.38,1335.36, 1259.72, 1222.02, 1180.06, 1146.08, 1100.19, 1084.69, 1030.56,990.29, 958.18, 936.74, 813.63, 789.81, 750.14, 695.10, 635.82, 598.89,570.61, 516.06, 492.85, 463.07, 446.22, 430.81.

Synthesis of Complex 12

2,6-difluoro-N,N-diphenylpyridin-4-amine (12a)

A Schlenk flask was loaded with diphenylamine (1.41 mL, 10.0 mmol, 1.0equiv.) and a stir-bar. The flask was filled with THF (30 mL) from SPS.Then the flask was connected to a Schlenk line under N₂, sealed with arubber septum and cooled in an ice-water bath. 1.6M n-butyllithiumsolution in hexane (6.25 mL, 10.0 mmol, 1.0 equiv.) was added dropwiseto the flask using a syringe through the septum. The resulting mixturewas stirred at room temperature for one hour. Another Schlenk flask wasloaded with 2,4,6-trifluoropyridine (10.0 mL, 113.0 mmol, 11.3 equiv.)and a stir-bar and filled with THF (70 mL) from SPS. Then the flask wasconnected to a Schlenk line under N₂, sealed with a rubber septum andcooled in an ice-water bath. The resulting solution from the first flaskwas cannula transferred to the second flask, and the reaction mixturewas stirred at room temperature for six hours. Brine solution (50 mL)was added to the reaction mixture, dichloromethane (3×50 mL) was used toextract the aqueous phase. Combined organic part was dried overanhydrous MgSO₄, filtered, and the filtrate was concentrated to get thecrude product. Recrystallization of the crude product from methanol gavethe product (12a) as white solid (1.56 g, 5.526 mmol) with a 55% yield.¹H-NMR (500 MHz, CDCl₃, ppm): δ 7.42-7.39 (m, 4H); 7.29-7.22 (m, 6H);6.08 (s, 2H). {¹H}¹³C-NMR (CDCl₃, 126 MHz, ppm): δ 163.17 (dd,J_(CF,CF)=21, 240 Hz); 160.94 (t, J_(CF)=12 Hz); 144.33; 130.26; 127.25;127.00; 92.69. ¹⁹F-NMR (CDCl₃, 339 MHz, ppm): δ −70.18.

This reaction was done with extreme precaution under a completely inertatmosphere.

2,6-di(1H-imidazol-1-yl)-N,N-diphenylpyridin-4-amine (12b)

Synthesis is similar as that of 9a.2,6-di(1H-imidazol-1-yl)-N,N-diphenylpyridin-4-amine (12b) was obtainedas white solid (0.304 g, 0.803 mmol) with 63% yield. ¹H-NMR (CDCl₃, 360MHz, ppm): δ 8.18 (s, 2H); 7.47-7.44 (m, 6H); 7.34-7.28 (m, 4H); 7.25(s, 2H); 7.13 (s, 2H); 6.59 (s, 2H). {¹H}¹³C-NMR (CDCl₃, 126 MHz, ppm):δ 158.47; 149.35; 144.26; 135.15; 130.71; 130.38; 127.10; 127.08;116.30; 97.76.

1,1′-(4-(diphenylamino)pyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium)triflate(12c)

Synthesis is similar as that of 9b.1,1′-(4-(diphenylamino)pyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium)triflate(12c) was obtained as white solid (0.410 g, 0.581 mmol) with 88% yield.¹H-NMR (DMSO-d6, 360 MHz, ppm): δ 10.00 (s, 2H); 8.56 (m, 2H); 7.95 (m,2H); 7.55-7.51 (m, 4H); 7.42-7.36 (m, 6H); 7.12 (s, 2H); 3.93 (s, 6H).{¹H}¹³C-NMR (DMSO-d6, 126 MHz, ppm): δ 158.90; 146.32; 143.54; 136.04;130.57; 127.43; 126.95; 124.57; 120.66 (q, J_(CF)=323 Hz); 119.32;100.34; 36.38. ¹⁹F-NMR (DMSO-d6, 339 MHz, ppm): δ −77.76.

Ru-[{Im(Me)-py(4-NPh₂)-Im(Me)}(CH₃CN)₂Cl]triflate (12)

Synthesis is similar as that of 9.Ru-[{Im(Me)-py(4-NPh₂)-Im(Me)}(CH₃CN)₂Cl]triflate (12) was obtained asyellow solid (0.057 g, 0.073 mmol) with 47% yield. ¹H-NMR (DMSO-d6, 360MHz, ppm): δ 8.26 (d, 2H, J_(HH)=2.2 Hz); 7.53 (d, 2H, J_(HH)=2.2 Hz);7.52-7.47 (m, 4H); 7.36-7.31 (m, 6H); 7.00 (s, 2H); 4.07 (s, 6H); 2.70(s, 3H); 2.14 (s, 3H). ¹⁹F-NMR (DMSO-d6, 339 MHz, ppm): δ −77.76. HRMS(ESI) calculated for RuC₂₉H₂₈N₈Cl (M-triflate): 625.1169, found625.1174. Anal. calculated for RuC₃₀H₃₀N₈O₄F₃SCl (M+H₂O): C—45.48,H—3.82, N—14.14; found C—46.07, H—3.76, N—14.36. FT-IR (ATR, cm⁻¹):3850.66, 3156.03, 3071.03, 2977.32, 2284.93, 2273.62, 2168.24, 2088.57,2047.02, 1977.58, 1639.21, 1597.93, 1564.24, 1536.35, 1482.12, 1440.69,1400.78, 1347.15, 1321.68, 1306.10, 1257.21, 1224.57, 1149.62, 1087.49,1077.18, 1062.64, 1030.55, 996.23, 963.15, 943.58, 916.61, 849.71,803.85, 788.07, 771.32, 752.66, 732.24, 721.02, 709.30, 693.29, 639.29,593.69, 571.89, 553.16, 516.85, 500.14, 466.44, 444.15, 429.38, 408.51.

Synthesis of complex 13 (1^(OH))

2,6-difluoropyridin-4-ol (13a) (Maleczka, R. E.; et al., Journal of theAmerican Chemical Society 2003, 125 (26), 7792-7793).

A Schlenk flask was loaded with 2,6-difluoropyridine (0.79 mL, 8.690mmol, 1.0 equiv.), pinacolborane (2.52 mL, 17.380 mmol, 2.0 equiv.),[Ir(COD)Cl]₂ (0.058 g, 1 mol %), DPPE (0.069 g, 2 mol %), dry THF (25mL) and a stir-bar inside a glove-box. The flask was sealed with arubber septum and taken out of the glove-box. Then the flask wasconnected to a Schlenk line under N₂, and the reaction mixture washeated at 80° C. while stirring for 16 hours. After cooling to roomtemperature, an aqueous solution (50 mL) of K-Oxone (5.88 g, 19.118mmol, 2.2 equiv.) was added slowly, stirring continued for 10 minutes.Then saturated aqueous solution (50 mL) of NaHSO₃ was added to quenchthe excess K-oxone. The resulting mixture was extracted with ethylacetate (3×50 mL), combined ethyl acetate part was washed with brine,dried over anhydrous MgSO₄, filtered and evaporated to get the crudeproduct. Crude was purified by column chromatography (silica gel) using0-30% ethyl acetate in hexane as eluent to obtain the product (13a) aswhite solid (0.83 g, 6.344 mmol) with 73% yield. ¹H-NMR (DMSO-d6, 500MHz, ppm): δ 11.90 (s, 1H); 6.40 (s, 2H). {¹H}¹³C-NMR (DMSO-d₆, 126 MHz,ppm): δ 171.66 (t, J_(CF)=12.9 Hz), 162.18 (dd, J_(CF,CF)=238, 22 Hz);93.49 (m). ¹⁹F-NMR (DMSO-d6, 339 MHz, ppm): δ −70.66.

2,6-difluoropyridin-3-ol was formed as a minor product.

4-(benzyloxy)-2,6-difluoropyridine (13b)

A Schlenk flask was loaded with 2,6-difluoropyridin-4-ol (0.7 g, 5.340mmol, 1.0 equiv.), K₂CO₃ (1.48 g, 10.680 mmol, 2.0 equiv.), TBAI (0.04g, 2 mol %) and a stir-bar. The flask was filled with DMF (15 mL) fromSPS. Then the flask was connected to a Schlenk line under N₂ and sealedwith a rubber septum. Benzylchloride (1.23 mL, 10.680 mmol, 2.0 equiv.)was added to the flask dropwise using a syringe through the septum. Thenthe reaction mixture was stirred at room temperature for 16 hours. After16 hours, cold water (20 mL) was added to the reaction mixture and wasextracted with ethyl acetate (3×50 mL), combined ethyl acetate part waswashed with brine, dried over anhydrous MgSO₄, filtered and evaporatedto get the crude product. Finally, the crude was purified by column(silica gel) chromatography using 0-12% ethyl acetate in hexane toobtain the product (13b) as white solid (1.03 g, 4.638 mmol) with 76%yield. ¹H-NMR (CDCl₃, 500 MHz, ppm): δ 7.44-7.37 (m, 5H); 6.37 (s, 2H);5.13 (s, 2H). {¹H}¹³C-NMR (CDCl₃, 126 MHz, ppm): δ 171.62 (t, 11.8 Hz),162.98 (dd, J_(CF, CF)=246, 20.2 Hz), 134.69; 129.06; 128.97; 127.72;93.07 (m); 71.41. ¹⁹F-NMR (CDCl₃, 339 MHz, ppm): δ −67.88.

4-(benzyloxy)-2,6-di(1H-imidazol-1-yl)pyridine (13c)

Synthesis is similar as that of 9a.4-(benzyloxy)-2,6-di(1H-imidazol-1-yl)pyridine (5c) was obtained aswhite solid (1.06 g, 3.336 mmol) with 82% yield. ¹H-NMR (CDCl₃, 500 MHz,ppm): δ 8.30 (m, 2H); 7.58 (m, 2H); 7.44-7.38 (m, 5H); 7.19 (m, 2H);6.82 (s, 2H); 5.24 (s, 2H). {¹H}¹³C-NMR (CDCl₃, 126 MHz, ppm): 169.24;149.75; 135.16; 134.65; 131.05; 129.12; 129.04; 127.67; 116.28; 97.01;71.24.

1,1′-(4-(benzyloxy)pyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium)triflate(13d)

Synthesis is similar as that of 9b.1,1′-(4-(benzyloxy)pyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium)triflate(13d) was obtained as white solid (1.12 g, 0.174 mmol) with 92% yield.¹H-NMR (DMSO-d6, 500 MHz, ppm): δ 10.21 (s, 2H); 8.72 (m, 2H); 8.04 (m,2H); 7.95 (s, 2H); 7.57-7.42 (m, 5H); 5.46 (s, 2H); 4.02 (s, 6H).{¹H}¹³C-NMR (DMSO-d6, 126 MHz, ppm): δ 170.16; 146.67; 136.19; 134.73;128.79; 128.74; 128.39; 125.01; 120.66 (q, J_(CF)=323 Hz); 119.08;101.02; 71.71; 36.61. ¹⁹F-NMR (DMSO-d6, 339 MHz, ppm): δ −77.76.

Ru-[{Im(Me)-py(4-OCH₂Ph)-Im(Me)}(CH₃CN)₂Cl]triflate (13e)

Synthesis is similar as that of 9.Ru-[{Im(Me)-py(4-OCH₂Ph)-Im(Me)}(CH₃CN)₂Cl]triflate (13e) was obtainedas greenish-yellow solid (0.126 g, 0.177 mmol) with 57% yield. ¹H-NMR(DMSO-d6, 360 MHz, ppm): δ 8.41 (d, J_(HH)=2.2 Hz, 2H); 7.72 (s, 2H);7.64 (d, J_(HH)=2.2 Hz, 2H); 7.58-7.42 (m, 5H); 5.38 (s, 2H); 4.11 (s,6H); 2.72 (s, 3H); 2.11 (s, 3H). ¹⁹F-NMR (DMSO-d6, 339 MHz, ppm): δ77.75. Anal. calculated for RuC₂₅H₂₅N₇O₄F₃SCl: C—42.11, H—3.53, N—13.75,found C—41.62, H—3.52, N—13.58. FT-IR (ATR, cm⁻¹): 3493.80, 3082.72,3044.90, 2928.50, 2269.95, 2110.27, 1629.93, 1578.90, 1551.58, 1483.39,1402.87, 1386.57, 1348.91, 1257.11, 1238.18, 1219.78, 1208.13, 1148.22,1101.20, 1084.67, 1065.60, 1029.86, 965.55, 916.46, 894.45, 842.70,788.57, 743.97, 733.72, 698.76, 655.66, 635.39, 597.34, 571.07, 516.04,444.46, 429.56.

Ru-[{Im(Me)-py(4-OH)-Im(Me)}(CH₃CN)₂Cl]triflate (13 (the same as1^(OH)))

Ru-[{Im(Me)-py(4-OCH₂Ph)-Im(Me)}(CH₃CN)₂Cl]triflate (0.120 g, 0.168mmol, 1.0 equiv.) was dissolved in acetonitrile (20 mL) in a two neckedround bottomed flask containing a stir bar. The flask was sealed with avacuum adapter and a rubber septum. Then the solution was purged with N2gas for 10 minutes while stirring, and 10% Pd—C (0.020 g) was added tothe flask. The head-space of the flask was evacuated and filled backwith H₂ gas using an H₂ filled balloon, and this process was repeatedthree times. The resulting mixture was stirred at room temperature underH₂ gas for 10 hours. After 10 hours, the reaction mixture was filteredthrough a celite plug to remove Pd—C, more acetonitrile (20 mL) was usedto wash the celite plug. The filtrate was concentrated to get agreenish-yellow solid, which was washed with acetonitrile (1 mL) anddiethyl ether (5 mL) three times to obtain the product (13 (1^(OH))) asa greenish-yellow solid (0.08 g, 0.129 mmol) with 77% yield. Singlecrystal was grown by slow vapor diffusion of diethyl ether intoacetonitrile solution of the compound. ¹H-NMR (DMSO-d6, 500 MHz, ppm): δ8.31 (s, 2H); 7.60 (s, 2H); 7.18 (s, 2H); 4.09 (s, 6H); 2.70 (s, 3H);2.11 (s, 3H). ¹⁹F-NMR (DMSO-d₆, 339 MHz, ppm): δ −77.75. HRMS (ESI)calculated for RuC₁₇H₁₉ON₇Cl (M-triflate): 474.0383, found 473.0372.Anal. calculated for RuC₁₈H₂₁N₇O₅F₃SCl: C—33.73, H—3.30, N—15.30; foundC—34.85, H—3.39, N—15.69. FT-IR (ATR, cm⁻¹): 3097.64, 2980.71, 2274.48,1632.75, 1590.71, 1566.04, 1500.01, 1478.34, 1404.49, 1347.56, 1254.77,1239.76, 1221.74, 1207.92, 1156.49, 1098.84, 1026.84, 948.70, 898.73,850.01, 819.26, 791.94, 743.38, 697.36, 635.44, 599.59, 571.43, 516.36,443.05, 422.36.

Other advantages which are obvious and which are inherent to theinvention will be evident to one skilled in the art. It will beunderstood that certain features and sub-combinations are of utility andmay be employed without reference to other features andsub-combinations. This is contemplated by and is within the scope of theclaims. Since many possible embodiments may be made of the inventionwithout departing from the scope thereof, it is to be understood thatall matter herein set forth or shown in the accompanying drawings is tobe interpreted as illustrative and not in a limiting sense.

The claims are not intended to include, and should not be interpreted toinclude, means-plus- or step-plus-function limitations, unless such alimitation is explicitly recited in a given claim using the phrase(s)“means for” or “step for,” respectively.

In view of the described processes and compositions, hereinbelow aredescribed certain more particularly described aspects of the inventions.These particularly recited aspects should not, however, be interpretedto have any limiting effect on any different claims containing differentor more general teachings described herein, or that the “particular”aspects are somehow limited in some way other than the inherent meaningsof the language and formulas literally used therein.

ASPECTS

Aspect 1: A method comprising: selectively deoxygenating at least oneoxygenated aromatic compound in the presence of a hydrogen gas and acatalyst system to form a reaction product, wherein the catalyst systemcomprises a catalyst of formula (I):

-   -   wherein,    -   R¹ is hydrogen, OH, O⁻, halogen, amine, C₁-C₁₀ alkyl, C₁-C₁₀        alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃        heteroaryl, C₆-C₁₄ aryloxy, C₃-C₁₀ cycloalkyl, or C₃-C₁₀        cycloalkenyl, wherein R¹ is optionally substituted with C₁-C₁₀        alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄        aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic acid,        ester, ether, halide, hydroxy, ketone, nitro, cyano, silyl,        sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol, phosphonyl;    -   each R² is, independent of the other, C₁-C₁₀ alkyl, C₂-C₁₀        alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃ heteroaryl,        wherein R² is optionally substituted with C₁-C₁₀ alkyl, C₁-C₁₀        alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃        heteroaryl, aldehyde, amino, carboxylic acid, ester, ether,        halide, hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo,        sulfonyl, sulfone, sulfoxide, or thiol,    -   each R³ and R⁴ are, independent of the other, hydrogen, C₁-C₁₀        alkyl, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃        heteroaryl, wherein R³ and R⁴ are optionally substituted with        C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl,        C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic        acid, ester, ether, halide, hydroxy, ketone, nitro, cyano,        silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol, or R³        and R⁴ combine together with the atoms to which they are        attached to form a cycloalkyl, cycloheteroaryl, aryl, or        heteroaryl;    -   each R¹⁶ and R¹⁷ are, independent of the other, hydrogen, OH,        O⁻, halogen, amine, C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl,        C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, C₆-C₁₄ aryloxy,        C₃-C₁₀ cycloalkyl, or C₃-C₁₀ cycloalkenyl, wherein each R¹⁶ and        R₁₅, independent of the other, is optionally substituted with        C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl,        C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic        acid, ester, ether, halide, hydroxy, ketone, nitro, cyano,        silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol, or        phosphonyl;    -   M is Ru or Ir;    -   each L is independently selected from Cl, Br, CH₃CN, DMF, H₂O,        bipyridine, phenylpyridine, CO₂, and a CNC-pincer ligand; and    -   n is 1, 2, or 3.

Aspect 2: The method of Aspect 1, wherein the oxygenated aromaticcompound has a formula (II)

-   -   wherein    -   R⁵ is independently selected from hydrogen, substituted or        unsubstituted C₆-alkyl, R¹¹—OH; —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹        substituted or unsubstituted C₃-C₁₀ cycloalkyls and        heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;    -   R⁶ is independently selected from hydrogen, hydrogen,        substituted or unsubstituted R¹¹—OH; —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,        substituted or unsubstituted C₃-C₁₀ cycloalkyls and        heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;    -   R⁷ is independently selected from hydrogen, substituted or        unsubstituted C₆-alkyl, R¹¹—OH, —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,        substituted or unsubstituted C₃-C₁₀ cycloalkyls and        heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;    -   R⁸ is independently selected from hydrogen, substituted or        unsubstituted C₆-alkyl, R¹¹—O_(H); —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,        substituted or unsubstituted C₃-C₁₀ cycloalkyls and        heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;    -   R⁹ is independently selected from hydrogen, substituted or        unsubstituted C₆-alkyl, R¹¹—OH; —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,        substituted or unsubstituted C₃-C₁₀ cycloalkyls and        heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;    -   R¹⁰ is independently selected from hydrogen, substituted or        unsubstituted C₆-alkyl, R¹¹—OH; —OR¹², R¹⁸OR¹⁹, R²⁰COR²¹,        substituted or unsubstituted C₃-C₁₀ cycloalkyls and        heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;    -   wherein when R⁶, R⁷, R⁹, and R¹⁰ are all hydrogen, R⁵ is R¹¹—OH,        R¹⁸OR¹⁹, or R²⁰COR²¹,    -   wherein R¹¹ is a bond, substituted or unsubstituted C₁-C₆ alkyl,        C₂-C₁₀ alkenyl, or Ar″;    -   R¹² is independently selected from hydrogen, substituted or        unsubstituted C₁-C₆ alkyl, C₂-C₁₀ alkenyl, and Ar′″,    -   R¹⁸ is independently selected from substituted or unsubstituted        C₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀ cycloalkyls and        heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;    -   R¹⁹ is independently selected from substituted or unsubstituted        C₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀ cycloalkyls and        heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;    -   R²⁰ is independently selected from a bond, substituted or        unsubstituted C₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀        cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, and Ar′;    -   R²¹ is independently selected from hydrogen, hydroxyl, C₁-C₁₀        alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄        aryl, C₁-C₁₃ heteroaryl, C₆-C₁₄ aryloxy, C₃-C₁₀ cycloalkyl, or        C₃-C₁₀ cycloalkenyl and Ar′, wherein R²¹ is optionally        substituted with C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl,        C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino,        carboxylic acid, ester, ether, halide, hydroxy, ketone, nitro,        cyano, silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol,        phosphonyl;    -   Ar′ is a C₆-C₁₄ aryl or heteroaryl group optionally substituted        with 1, 2, or 3 optional substituents; and    -   Ar″ is a C₆-C₁₄ aryl or heteroaryl group optionally substituted        with 1, 2, or 3 optional substituents;    -   Ar′″ is a C₆-C₁₄ aryl or heteroaryl group optionally substituted        with 1, 2, or 3 optional substituents;    -   wherein Ar′, Ar″, or Ar′″, are the same or different.

Aspect 3: The method of Aspect 2, wherein R⁵ is R¹¹—OH, R¹⁸OR¹⁹, orR²⁰COR²¹, R⁶ is independently selected from hydrogen, substituted orunsubstituted R¹¹—OH; —OR¹², substituted or unsubstituted C₃-C₁₀cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R⁷ isindependently selected from hydrogen, substituted or unsubstitutedR¹¹—OH; —OR¹², substituted or unsubstituted C₃-C₁₀ cycloalkyls andheteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R⁸ is independently selected fromhydrogen, substituted or unsubstituted R¹¹—OH; —OR¹², substituted orunsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, andAr′; wherein R⁹ is independently selected from hydrogen, substituted orunsubstituted R¹¹—OH; —OR¹², substituted or unsubstituted C₃-C₁₀cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R¹⁰ isindependently selected from hydrogen, substituted or unsubstitutedC₁-C₆-alkyl, R¹¹—OH; —OR¹², substituted or unsubstituted C₃-C₁₀cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R¹¹ is a bond,substituted or unsubstituted C₁-C₆ alkyl, C₂-C₁₀ alkenyl, or Ar″; R¹² isindependently selected from hydrogen, substituted or unsubstituted C₁-C₆alkyl, C₂-C₁₀ alkenyl, and Ar′″, R¹⁸ is independently selected fromsubstituted or unsubstituted C₁-C₆-alkyl, substituted or unsubstitutedC₃-C₁₀ cycloalkyls and heteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R¹⁹ isindependently selected from substituted or unsubstituted C₁-C₆-alkyl,substituted or unsubstituted C₃-C₁₀ cycloalkyls and heteroalkyls, C₂-C₁₀alkenyl, and Ar′; R²⁰ is independently selected from a bond, substitutedor unsubstituted substituted or unsubstituted C₃-C₁₀ cycloalkyls andheteroalkyls, C₂-C₁₀ alkenyl, and Ar′; R²¹ is independently selectedfrom hydrogen, hydroxyl, C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl,C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, C₆-C₁₄ aryloxy, C₃-C₁₀cycloalkyl, or C₃-C₁₀ cycloalkenyl and Ar′, wherein R²¹ is optionallysubstituted with C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylicacid, ester, ether, halide, hydroxy, ketone, nitro, cyano, silyl,sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol, phosphonyl; Ar′ is aC₆-C₁₄ aryl or heteroaryl group optionally substituted with 1, 2, or 3optional substituents; Ar″ is a C₆-C₁₄ aryl or heteroaryl groupoptionally substituted with 1, 2, or 3 optional substituents; Ar′″ is aC₆-C₁₄ aryl or heteroaryl group optionally substituted with 1, 2, or 3optional substituents; and wherein Ar′, Ar″, and Ar′″ are the same ordifferent.

Aspect 4: The method of Aspect 2 or 3, wherein the aromatic compound offormula (II) comprises at least two hydroxyl groups.

Aspect 5: The method of any one of Aspects 3-4, wherein the aromaticcompound of formula (II) is selected from

-   -   wherein R^(11′) is a bond, substituted or unsubstituted C₁-C₆        alkyl, C₂-C₁₀ alkenyl, and Ar″; and    -   wherein R^(11′) and R¹¹ are the same or different.

Aspect 6: The method of Aspect 5, wherein R^(11′) and R¹¹ are not thesame.

Aspect 7: The method of any one of Aspects 1-6, wherein R¹ is hydrogen,OH, O⁻, halogen, or optionally substituted amine, alkyl, aryl, alkoxy,or aryloxy.

Aspect 8: The method of any one of Aspects 1-7, wherein R³ and R⁴combine together with the atoms to which they are attached to form anaryl or heteroaryl.

Aspect 9: The method of any one of Aspects 1-8, wherein R³ and R⁴ areboth hydrogen.

Aspect 10: The method of any one of Aspects 1-9, wherein M is Ru or Ir.

Aspect 11: The method of any one of Aspects 1-10, wherein at least one Lis Cl, Br, CH₃CN, DMF, H₂O, bipyridine or phenylpyridine.

Aspect 12: The method of any one of Aspects 1-11, wherein the catalystis

wherein R″ is methyl or phenyl, and X is Cl, Br, or CH₃CN, wherein n=1when X is Cl or Br and n=2 when X is CH₃CN.

Aspect 13: The method of any one of Aspects 1-12, further comprising oneor more counteranions selected from I⁻, Br⁻, CF₃COO⁻, BF₄ ⁻, OTf⁻, orPF₆ ⁻.

Aspect 14: The method of any one of Aspects 1-13, wherein the catalystsystem further comprises an external acid or base.

Aspect 15: The method of any one of Aspects 1-14, wherein the catalystsystem does not comprise an external acid.

Aspect 16: The method of Aspect 14 or 15, wherein the base comprises aninorganic base or organic base.

Aspect 17: The method of any one of Aspects 14-16, wherein the basecomprises a strong base, a weak base, or a Lewis base.

Aspect 18: The method of any one of Aspects 3-17, wherein the reactionproduct comprises a compound A of formula (III)

wherein R¹³ is R¹¹—H.

Aspect 19: The method of Aspect 18, wherein when the aromatic compoundof formula (II) is selected from

the compound A comprises:

Aspect 20: The method of any one of Aspects 3-19, wherein the reactionproduct further comprises a compound B of formula (IV):

-   -   wherein R¹⁴ is —OR¹⁵, wherein R¹⁵ is C₁-C₁₀ alkyl.

Aspect 21: The method of Aspect 20, wherein when the aromatic compoundof formula (II) is selected from

-   -   the compound B comprises:

Aspect 22: The method of any one of Aspects 19-21, wherein the compoundA is selectively formed over the compound B.

Aspect 23: The method of any one of Aspects 19-22, wherein theselectivity of the compound A is from about 50% to 100%.

Aspect 24: The method of any one of Aspects 19-23, wherein the compoundA has a yield from about 50% to 100%.

Aspect 25: The method of Aspect 24, wherein the compound A has a yieldfrom about 85% to 100%.

Aspect 26: The method of Aspect 23, wherein the selectivity of thecompound A is from about 85% to 100%.

Aspect 27: The method of any one of Aspects 1-24, wherein the catalystis present in an amount of greater than 0 mol % to about 1.5 mol %.

Aspect 28: The method of any one of Aspects 14-27, wherein the base ispresent in an amount from about 50 mol % to 100 mol %.

Aspects 29: A catalyst of formula (I):

-   -   wherein,    -   R¹ is hydrogen, OH, O⁻, halogen, amine, C₁-C₁₀ alkyl, C₁-C₁₀        alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃        heteroaryl, C₆-C₁₄ aryloxy, C₃-C₁₀ cycloalkyl, or C₃-C₁₀        cycloalkenyl, wherein R¹ is optionally substituted with C₁-C₁₀        alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄        aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic acid,        ester, ether, halide, hydroxy, ketone, nitro, cyano, silyl,        sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol, or phosphonyl;    -   each R² is, independent of the other, C₁-C₁₀ alkyl, C₂-C₁₀        alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃ heteroaryl,        wherein R² is optionally substituted with C₁-C₁₀ alkyl, C₁-C₁₀        alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃        heteroaryl, aldehyde, amino, carboxylic acid, ester, ether,        halide, hydroxy, ketone, nitro, cyano, silyl, sulfo-oxo,        sulfonyl, sulfone, sulfoxide, or thiol,    -   each R³ and R⁴ are, independent of the other, hydrogen, C₁-C₁₀        alkyl, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃        heteroaryl, wherein R³ and R⁴ are optionally substituted with        C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl,        C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic        acid, ester, ether, halide, hydroxy, ketone, nitro, cyano,        silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol, or R³        and R⁴ combine together with the atoms to which they are        attached to form a cycloalkyl, cycloheteroaryl, aryl, or        heteroaryl;    -   each R¹⁶ and R¹⁷ are, independent of the other, hydrogen, OH,        O⁻, halogen, amine, C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl,        C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, C₆-C₁₄ aryloxy,        C₃-C₁₀ cycloalkyl, or C₃-C₁₀ cycloalkenyl, wherein each R¹⁶ and        R₁₅, independent of the other, is optionally substituted with        C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl,        C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylic        acid, ester, ether, halide, hydroxy, ketone, nitro, cyano,        silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol,        phosphonyl;    -   M is Ru or Ir;    -   each L is independently selected from Cl, Br, CH₃CN, DMF, H₂O,        bipyridine, phenylpyridine, CO₂, and a CNC-pincer ligand; and    -   n is 1, 2, or 3.

Aspect 30: The catalyst of Aspect 29, selected from

wherein R″ is methyl or phenyl, and X is Cl, Br, or CH₃CN, wherein n=1when X is Cl or Br, and n=2 when X is CH₃CN.

The invention claimed is:
 1. A method comprising: selectivelydeoxygenating at least one oxygenated aromatic compound in the presenceof a hydrogen gas and a catalyst system to form a reaction product,wherein the catalyst system comprises a complex of formula (I):

wherein R¹ is hydrogen, OH, halogen, amine, C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy,C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, C₆-C₁₄aryloxy, C₃-C₁₀ cycloalkyl, or C₃-C₁₀ cycloalkenyl, wherein R¹ isoptionally substituted with C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl,C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino,carboxylic acid, ester, ether, halide, hydroxy, ketone, nitro, cyano,silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol, phosphonyl; eachR² is, independent of the other, C₁-C₁₀ alkyl, C₂-C₁₀ alkenyl, C₂-C₁₀alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃ heteroaryl, wherein R² is optionallysubstituted with C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino, carboxylicacid, ester, ether, halide, hydroxy, ketone, nitro, cyano, silyl,sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol; each R³ and R⁴ are,independent of the other, hydrogen, C₁-C₁₀ alkyl, C₂-C₁₀ alkenyl, C₂-C₁₀alkynyl, C₆-C₁₄ aryl, or C₁-C₁₃ heteroaryl, wherein R³ and R⁴ areoptionally substituted with C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl,C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino,carboxylic acid, ester, ether, halide, hydroxy, ketone, nitro, cyano,silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol, or R³ and R⁴combine together with the atoms to which they are attached to form acycloalkene ring, heteroaromatic ring, or aromatic ring; each R¹⁶ andR¹⁷ are, independent of the other, hydrogen, OH, halogen, amine, C₁-C₁₀alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, C₆-C₁₄ aryl,C₁-C₁₃ heteroaryl, C₆-C₁₄ aryloxy, C₃-C₁₀ cycloalkyl, or C₃-C₁₀cycloalkenyl, wherein each R¹⁶ and R₁₅, independent of the other, isoptionally substituted with C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, C₂-C₁₀ alkenyl,C₂-C₁₀ alkynyl, C₆-C₁₄ aryl, C₁-C₁₃ heteroaryl, aldehyde, amino,carboxylic acid, ester, ether, halide, hydroxy, ketone, nitro, cyano,silyl, sulfo-oxo, sulfonyl, sulfone, sulfoxide, thiol, or phosphonyl; Mis Ru or Ir; each L is independently selected from C₁, Br, CH₃CN, DMF,H₂O, bipyridine, phenylpyridine, CO₂, and a CNC-pincer ligand; and n is1, 2, or 3; wherein the oxygenated aromatic compound has the formula:

wherein R⁶ is independently selected from hydrogen, substituted orunsubstituted C₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀cycloalkyl and heteroalkyl, C₂-C₁₀ alkenyl, and Ar′; R⁷ is independentlyselected from hydrogen, substituted or unsubstituted C₁-C₆-alkyl,substituted or unsubstituted C₃-C₁₀ cycloalkyl and heteroalkyl, C₂-C₁₀alkenyl, and Ar′; R⁸ is independently selected from hydrogen,substituted or unsubstituted C₁-C₆-alkyl, substituted or unsubstitutedC₃-C₁₀ cycloalkyl and heteroalkyl, C₂-C₁₀ alkenyl, and Ar′; R⁹ isindependently selected from hydrogen, substituted or unsubstitutedC₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀ cycloalkyl andheteroalkyl, C₂-C₁₀ alkenyl, and Ar′; R¹⁰ is independently selected fromhydrogen, substituted or unsubstituted C₁-C₆-alkyl; substituted orunsubstituted C₃-C₁₀ cycloalkyl and heteroalkyl, C₂-C₁₀ alkenyl, andAr′; wherein R¹¹ is a bond, substituted or unsubstituted C₁-C₆ alkylene,C₂-C₁₀ alkenylene, or Ar″; R¹⁸ is independently selected fromsubstituted or unsubstituted C₁-C₆-alkylene, C₂-C₁₀ alkenylene, and Ar″;R¹⁹ is independently selected from substituted or unsubstitutedC₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀ cycloalkyl andheteroalkyl, C₂-C₁₀ alkenyl, and Ar′; Ar′ is a C₆-C₁₄ aryl or heteroarylgroup optionally substituted with 1, 2, or 3 substituents; Ar″ is aC₆-C₁₄ arylene or heteroarylene group optionally substituted with 1, 2,or 3 substituents; wherein Ar′ and Ar″ are the same or different, andwherein the reaction product has the formula:


2. The method of claim 1, wherein R⁶ is independently selected fromhydrogen, substituted or unsubstituted C₁-C₆-alkyl, substituted orunsubstituted C₃-C₁₀ cycloalkyl and heteroalkyl, C₂-C₁₀ alkenyl, andAr′; R⁷ is independently selected from hydrogen, substituted orunsubstituted C₁-C₆-alkyl, substituted or unsubstituted C₃-C₁₀cycloalkyl and heteroalkyl, C₂-C₁₀ alkenyl, and Ar′; R⁸ is independentlyselected from hydrogen, substituted or unsubstituted C₁-C₆-alkyl,substituted or unsubstituted C₃-C₁₀ cycloalkyl and heteroalkyl, C₂-C₁₀alkenyl, and Ar′; wherein R⁹ is independently selected from hydrogen,substituted or unsubstituted C₁-C₆-alkyl, substituted or unsubstitutedC₃-C₁₀ cycloalkyl and heteroalkyl, C₂-C₁₀ alkenyl, and Ar′; R¹⁰ isindependently selected from hydrogen, substituted or unsubstituted C₁-C₆alkyl substituted or unsubstituted C₃-C₁₀ cycloalkyl and heteroalkyl,C₂-C₁₀ alkenyl, and Ar′; R¹¹ is a substituted or unsubstituted C₁-C₆alkylene.
 3. The method of claim 1, wherein R³ and R⁴ combined togetherwith the atoms to which they are attached, form an aromatic ring orheteroaromatic ring.
 4. The method of claim 1, wherein R³ and R⁴ areboth hydrogen.
 5. The method of claim 1, wherein at least one L is Cl,Br, CH₃CN, DMF, H₂O, bipyridine or phenylpyridine.
 6. The method ofclaim 1, wherein the catalyst is a complex having the formula:

wherein R″ is methyl or phenyl, and X is Cl, Br, or CH₃CN, wherein n=1when X is Cl or Br and n=2 when X is CH₃CN.
 7. The method of claim 6,wherein the catalyst system further comprises one or more counteranionsselected from I⁻, Br⁻, CF₃COO⁻, BF₄ ⁻, OTf⁻, or PF₆ ⁻.
 8. The method ofclaim 1, wherein the catalyst system further comprises an external acidor base, and wherein when the base is present, the base comprises aninorganic base or organic base in an amount from about 50 mol % to 100mol %.
 9. The method of claim 1, wherein the catalyst system does notcomprise an external acid.
 10. The method of claim 1, wherein thecatalyst is present in an amount of greater than 0 mol % to about 1.5mol %.